Updated on 9/19/2021.

This document is meant to serve as a general guide on beating Humankind on its highest difficulty. I love the Civilization series(really the 4x genre in general), and believe Humankind has the potential to exceed it in the future. I've beaten this game several times on its highest difficulty and wish to share my experiences. At the time this was written, the game has only recently released and is likely subject to much change - updates may invalidate much of what is written here.

As described here: https://humankind.fandom.com/wiki/Difficulty
Though the player suffers no penalty themselves, on the highest difficulty the AI are given the following bonuses:

+3 Food per Farmer on all Cities
+3 Industry per Worker on all Cities
+3 Money per Trader on all Cities
+3 Science per Researcher all on Cities
+60 Stability on all Cities
+2 Strength Combat Strength on all Units

Note that the FIMS bonuses are all flat values that scale with workers. Because these bonuses are flat rather than percentage based, they tend to not scale well. For example, early on in a city with with 9 population with 3 workers, the +9 industry would require potentially 3+ Industry Districts to offset. In contrast, if a late game AI city has 60 population, 15 of which are workers, that would amount to a +45 industry bonus. A +45 industry bonus is easily offset by half of a Strip Mine or a single Jama Masjid. What this means is that the player will be at a severe disadvantage early in the run, and due to the way the FIMS bonuses scale the run should in theory become easier over time.

The combat strength bonus is significant, and comparable to the difference between a given culture's emblematic unit and a normal unit(ie. swordsmen vs Shotelai) and basically impossible to offset during the neolithic/ancient era, and thus essentially means combat should be avoided during the first two eras. As the game progresses, electing to use the Professional Soldiers Civic and leaning towards the Homeland ideology axis will balance this deficit out.

The effect of the bonus stability is difficult to measure - but it almost certainly scales in such a manner that it decreases as the game progresses and you get access to more sources of stability. The strategy to compensate for this is mostly by trading for luxury resources.

The general strategy is thusly:
1. Do not engage in war early on(until classical at the earliest, usually medieval).
2. Establish trade for luxury resources.
3. Grab Agrarian and Builder cultures early on and scale into late game where AI FIMS bonuses fall off. Scaling is most easily accomplished by building wide rather than tall.
4. Win the game by acquiring as many stars/fame as possible. Please note that because of the way Fame works it is generally not optimal to immediately transcend cultures, as you will likely only earned a fraction of that era's available stars and thus miss out on opportunities to earn fame. It is very possible to end the game in a dominant position but still lose due to lack of fame.
5. After acquiring the most fame, trigger the end game condition (https://humankind.fandom.com/wiki/End_Condition). The fastest and most consistent is generally the science ending, whereby the game ends when all technologies are researched. If mid game conquest has progressed well, ensuring all other cultures have been eliminated or vassalized can arguably be faster, especially if the number of AIs is low.

Because of the outlined strategy chosen to compensate for the bonuses given to the AI, the following map settings will be optimal. I have however beaten the game on Humankind difficulty on a variety of settings. In order of importance:

World size: Huge
The actual answer is dependent upon the number of players, but generally speaking larger is better. Having a large amount of landmass also allows for more expansion before war is likely.
Minor cultures can also more easily spawn, allowing for a more diverse way to claim territory. Thus, if you're in a situation whereby you're forced to choose a non-optimal culture(such as a merchant culture), you can still use money to assimilate them.

World shape: Large Pangea
Facilitates ease of scouting and procurement of potential trading partners. The way deep and shallow waters works in this game often gates the player from interacting with other continents until at minimum Cogs are researched.

Land Percentage: 70-80%
Same reasoning as having a large pangea world shape with the caveat that you want enough ocean such that trading routes by ships is easily accessible. Not enough water and it can be easy to become land locked and unable to access trading partners to offset the stability bonuses.

Climate: New World
This setting ensures that a continent without existing cultures will spawn. The benefit of this is that the AI at the moment seems to be really poor at using naval units to expand, meaning that you'll likely be the first to claim the desirable territory in the New World. It also gives you a back up plan for if you end up getting boxed in early - beeline for Cogs and get more territory in a fresh continent.

Elevation: Flat
Flat elevation increases the speed at which scouting is done, and thus discovery of potential trading partners. Flat elevation however does tend to decrease flat industry yields which makes the AI FIMS bonus comparatively better. Something else of note is that flat terrain also tends to promote the use of cavalry, especially the ones with charge bonuses, as the increased mobility will allow them to proc those traits more often.

Game Speed: Slow/Endless
I've played most of my games on standard speed, however I've also noticed that the slower game speeds seem to be easier. A sample size of a few games however is difficult to make a convincing recommendation on, but is noted nonetheless.

General Strategy

1. Set your scouts to auto-explore. The AI at the moment does a fantastic job of finding stars. Feel free to interrupt auto-explore if you need to build an outpost or are hunting a nearby animal that only take 1 army to kill.
2. When your hunting party grows, turn off auto-explore, then split the party into two separate armies and send them in different directions. Turn auto-explore back on when they are sufficiently far apart. By the end of this era you should have 3+ armies.
3. When you reach the influence threshold for being able to place an outpost, do so in an area with a minimum of 10 food. Ideally with strategic/luxury resources on or adjacent to the territory. It is okay for you to spend several turns looking for an appropriate place, but you want the outpost to be completed by the time you choose your first culture.
4. Avoid hunting animals that take more than 1 party to kill unless you are out of things to explore(which can happen on small continents/islands, but should never happen if you're on a pangea), or if you're close to getting the hunter star.
5. Ransacking sanctuaries is generally worth it this early, as they should yield food when ransacked by nomads(hover over a tile when selecting the tile to ransack to see what they yield). The caveat is that they spawn animals which can potentially net you a faster hunter star if you leave them alone.
6. Food is king this early on. When events occur, prioritize the choices that give bonus food or if you're lucky an extra army.
7. DO NOT transcend to the next era without getting your neolithic legacy trait (https://humankind.fandom.com/wiki/Culture#Legacy_Trait):
Choose one from below
+1 Industry per Population on City or Outpost
+1 Food per Population on City or Outpost
+1 Science per Population on City or Outpost

I generally choose science, as science yields from terrain are basically non-existent and are difficult to compensate for early on. However if the locations you have scouted are low on food, the food option is suitable as well. Industry is less important than food in the very beginning and can easily be generated by exploiting the terrain.

After having the opportunity to talk with some other players who attempt to follow this guide, it seems that wars declared during the Ancient to Medieval era is the most common stumbling block. And indeed, the AI are the strongest at this point due to how their bonuses have an early game skew. I myself probably have a near 100% success rate with this strategy if I can get to the Early Modern Era without being more than 4k fame behind. The vast majority of my losses are due to poorly handled early game wars.

Here's a few tips I've added specifically with handling/avoiding early wars(Ancient to Medieval):

Avoiding the war:
1. Cultivate diplomatic relationships, this includes spending gold when they ask for it when proposing a treaty. A few hundred money early on is worth delaying a war later by several turns, or even outright preventing one. This is especially true for neighboring cultures.
2. Take note of the AI personas, take note of their attributes(militaristic, aggressive, etc...). Certain AI personas will rarely go to war(Tijibruke, Mama Ocllo), while others often will(Beowulf, Agammemnon, Gilgamesh). Expand towards those that are peaceful and away from the aggressive ones.
2a. Find Tijibruke and become his ally. This can be done consistently. This AI specifically is
incredibly easy to become allies with and will not break trade agreements set in place of his own
volition.
3. Commonly in the Medieval era, converting religions can avoid wars caused by 'suppressing the faithful' grievances.
4. Have units. Just build some even if you're not declaring war anytime soon. I don't know the exact details, but the AI very likely does army strength calculations before determining whether or not it will declare war.
5. If you REALLY don't like war, turn on the Peaceful Mode option in the difficulty menu. Though at this point we're basically not playing the same game anymore, but you can still get the relevant Humankind Difficulty achievements when you do this.

Fighting a war:
1. Become familiar with the combat modifiers: https://humankind.fandom.com/wiki/Combat#Combat_modifiers
Modifiers that are frequently abusable while defending are:
-High ground: +4 Strength Combat Strength
-Defending: +2 Strength Combat Strength
-Fortification: +6 Strength Combat Strength
-Garrison District: +1 Strength Combat Strength
-Crossing river: -3 Strength Combat Strength
If in a hypothetical scenario, you build a warrior(19 str), have him defend(+2) on high ground(+4) in a garrison district(+1) with fortifications(+6) = 32 strength
you can actually have him do well against units an entire era above yours, such as for example swordsman(25) with AI difficulty bonus(+2) and veterancy(+1-3) = 28-30 strength.

2. Build a Garrison Districts and Palisades. These two ensure you'll get the +6 strength Fortifications combat bonus consistently. This is the most consistently impactful bonus you can get defensively.
3. Usually being behind 1 era in terms of unit strength isn't a death sentence if you're defending, but being behind in tech AND being outnumbered is. I believe it's because it tends to be a lot easier to trigger flanking/Rear attack bonuses when you have more units. This isn't always possible, but if you're defending try to place districts/units in such a manner that you form choke points so the enemy cannot trigger these bonuses easily.
4. Upgrade your troops if you can. This will carry over their exp/veterancy levels. Second only to spending money on trading agreements, upgrading troops should be a significant money sink. You can even prepare for war by building a bunch precursor units and then upgrading them immediately when you get the tech/strategic resources required.
5. Auto-combat(AI automatically taking turns for you) and instant resolution(automatic calculation) can yield different results. Usually, if they're different, Auto-combat seems to yield better results. I usually try to avoid using either of these two options, especially if I have ranged/cavalry units, but sometimes for very large battles the AI will occasionally outperform me.
6. This is basically not possible during the Ancient/Classical eras, but during the medieval era if you've been good about scouting and have patronized independent peoples, you can hire their armies for Money. Independent people technology at this era is typically advanced enough that they can hold out defensively against an AI single handedly.

Losing a war:
1. If a war does break out, and the enemy is far superior to you, white peace/ff/become a vassal right away before you lose anything, so the difference between the enemy's and your war supports remains low. Often times you can get away with just paying them 700-2000 gold early on. This will likely bring your money to the negatives and make it difficult to afford trading for the rest of the Era, but is better than losing 2-3 territories.
2. When someone gets vassalized, the vassal gives up a percentage of its money every turn, both the liege and the vassal get access to each other's resources, and the liege controls the vassal's diplomatic relationships. If you're surrounded by aggressive AIs, paying some gold and giving access to resources to one of the AIs to prevent the others from declaring war on you can be worth it.

Cultures
High Priority:
Harappans: Food is key this early in the game, as most things this early on are gated by population. Of note, Agrarian Era stars seem to be the easiest to get, and by picking this culture you will be able to get them a rate fast enough to ensure an early pick of the next era's cultures. The runner is also a fantastic emblematic unit for the strategy we're using. It should be noted that the AI seems to prioritize the Harappans as a pick.
Olmecs: Again, food is key. Also, so is expansion, which the bonus influence points helps promote. In fact, the Olmecs might be a better choice than the Harappans on maps in which you anticipate early wars, as the Javelin Throwers are more useful than Runners during wartime. But if you're playing on the recommended settings this should not occur.
Egyptians: While not as important as food early on, industry is probably the most important FIMS resource overall. Both the emblematic trait and emblematic quarter are fantastic. The Markabata emblematic unit is solid, but requires horses which is not readily available this early in the game.

Medium Priority:
Mycenaeans: Provides no food, but some industry that can be quite significant with good placement. The cyclopean fortress also provides a large amount(+15) of stability and the emblematic trait scales well too(-20% unit industry cost, +25xp). The Promachoi are strong and do not require any strategic resource to build either. If you happen to settle close to AIs with good territories, or are anticipating something akin to an early Hun attack, perhaps even move the Mycenaeans up a slot or two.
Babylonians: Food is king during the ancient era and this culture provides some. Science is okay early on, providing no direct way to expand/grow our cities but opens up options faster. The emblematic unit works well as a defensive tool as well. The real issue is the emblematic trait scales terribly. At +2 science in the capital per researched technology, you're looking at something like +150-200 end game, which is worth a single Swedish Research Institute or maybe 4-5 research quarters. Another comparison for how poorly it scales is the fact that a lot of the end technologies cost between 15k-20k science to complete.
Zhou: Provides no bonus food or industry, but their emblematic trait is arguably the best of the Ancient Era ones. Stability is hard to come by until you can establish trade routes for those luxury resources, which is unlikely to occur this early. In fact, if you're playing on map settings whereby trade partners are very difficult to come by I would move Zhou up to High Priority. Also to be noted, the Zhanche with the high stability bonus have 26 strength(23+3) making them the most powerful ancient era unit in the game(Requiring both horse and copper however make them twice and difficult to access compared to the Markabata).
Nubians: I think gold is generally the worst FIMS resource, however if you end up in the rare situation whereby you can feasibly get 8-10+ resources between your first two cities, that translates to +40-50 gold per a turn via the emblematic trait, which would allow you to purchase a new district every 5-10 turns or so(depending on game speed). This ability also opens up a real possibility to go for the 2nd and 3rd tier merchant era stars for the classical era, which are normally out of reach for non-merchant cultures. A solid emblematic unit in additional to some production from the Meroe Pyramids makes this culture a niche middle tier.

Low Priority:
Assyrians: The +1 land movement is actually really good for scouting, which is important as we want those trade routes asap. Their emblematic unit requires horses, but can be useful for raiding, which can yield benefits without being at war. However, the emblematic quarter is not useful and provides no food or industry bonuses.
Hittites: The only real reason to go with the hittites is emblematic trait(+1 strength). Their emblematic unit is powerful, but requires horses, and you shouldn't be going to war this early anyway. Their emblematic quarter is pretty bad considering this early on you'll unlikely have more than 2 cities. The strengths of this culture just do not align with our strategy.
Phoenicians: The worst culture for the strategy we're using. Money is the worst FIMS resource, we're playing on pangea so the bireme is useless.

Wonders
1. Prioritize Pyramid of Giza if possible. District building on a pangea map makes this particularly good.
2. Hanging gardens if you have access to a resource that boosts industry/food.
The other two aren't worth the cost of their culture and industry.

General Guidelines
1. Upgrade your outpost to a city, and if able immediately attach available adjacent outposts. SWAP ALL CITIES FROM BALANCED POLICY TO CITY GROWTH. Disband nearby armies to increase city population, leaving 2-3 armies to auto-explore.
2. Continue to expand, prioritizing horse/copper if your emblematic units require those, followed by luxury resources. Food is key followed by industry. Expand towards neighbors if their AI traits are passive(try to cut them off), expand away if they have aggressive traits.
3. Makers quarters(or its equivalent) should be built first if settled area industry production is low(vice versa for food). If you find yourself low on industry because you've been prioritizing food, do not hesitate to chop down a few trees for a boost.
3. Any event choices should prioritize shifting the geopolitical axis towards Homeland. The rest are largely optional. Maybe prioritize Progress if you want to end the game via science.
4. When you receive the option to pick your faith, opt for shamanism if you were able to get one of the food producing cultures/get good food producing cities. In general, you can choose to engage with or avoid the religion mechanic as you see fit. Having your own religion allows for easy avenues to declare war later(oppressing the faithful), however if you just completely avoid the religion mechanic you can save whatever resources you might've spent on religion and will have an easier time forming alliances once you've changed religions to another culture's. Both options are viable, but I tend to at least build the first few early stone circles for the easy stability.
5. If you happen to find another culture, greet them and attempt to establish any sort of treaty if possible. This will given you a diplomacy bonus in the future and help you avoid war. Try to sign a trade agreement if possible. Do not engage in war.
6. When you trade, prioritize resources that give a flat bonus rather than a % one this early on. Prioritize food and industry bonuses.
7. DO NOT transcend until at minimum tier 2 of your affinity stars have been reached. The stars that match your affinity yield bonus fame, skipping out of them is a terrible. While you can transcend when you reach 7/21 available stars, aim for 9/21 before doing so. If you do not, you run the risk of ending the game without enough fame. You'll probably have 2+ scientist stars, and 2+ agrarian, so typically the focus on expansion/builder is what nets you the remaining stars. The AI FIMS bonus is the strongest at this point, you will likely be in the bottom third in terms of Fame.

Cultures
In general at this point you're looking for industry/influence/stability, and food if you didn't manage to secure any during the ancient era. Science is probably third on the FIMS priority list, followed by gold.

High Priority:
Maya: During the classical era, industry overtakes food as the most important FIMS resource. And the Maya delivers in spades. Fantastic trait, fantastic quarter, mediocre emblematic unit(though requires no resource) solidifies the Maya as a high priority pick.
Achaemenid Persians:
The trait is fantastic, the best of the Classic Era, possibly of the entire game. In fact, +2 max cities/+10 stability pretty much is the only reason they are this high. Everything else is mediocre.
Celts: While food is no longer as important in the classical era, it's still second only to industry. The early faith on the emblematic quarter also virtually guarantees you'll reach at minimum a tier 3 religion tenet. If you plan on avoiding the religion mechanic, move the Celts down a few picks. The Gaesati is rather mediocre, however requires no strategic resources.

Medium Priority:
Rome: Gives no industry bonuses, however has a solid classical era trait(especially if you've ignored money like this guide suggests), and an emblematic quarter that potentially offers lots of stability and influence. My favorite back up pick if luxury resources have not been secured. Praetorian Guards also are fantastic for their industry cost(the strongest non-cavalry unit in the Classical Era), but do require iron. If you've made trading a priority however, this can be obtained reasonably consistently. Requires you to be at war(and winning) to make the most of them however, so is a bit of a high-risk, high-reward faction. If you're not in a position to be winning wars, move the Romans down a a few picks.
Mauryans: A very good trait combined with an very good emblematic quarter makes it easy to expand with the Mauryans. It should be noted that their Saṃnāhya has the potential to be very good for their cost, but should be used in conjunction with melee units. Like with the Celts, the bonus religion virtually guarantees you'll reach tier 3 religion tenet, and it even gives a bit of science to boot. However, giving no industry/stability/food prevents this from being top tier choice.
Huns: Fantastic emblematic unit and trait. The unique way the Hunnic Horde works gives them the potential to be the strongest emblematic unit of the era. In fact, if your starting position dictates that you must go to war early, and you have access to horses, the Huns would be a high priority pick, especially if you have the Zhou emblematic unit already available. The lack of anything else of use however makes this series of options not optimal for our strategy.
Greeks: Offers a lot of science, which is mediocre this early on with this specific strategy. What prevents the Greeks from being lower on the list are the Hoplites. They require copper, however they beat every single cavalry unit in this era due to their anti-cavalry trait. If you get a set of 3 phalanxes that are adjacent to each other(which can be done consistently), that pushes their strength to 29(27+2), meaning they only really lose to the Praetorian Guards(30) who require Iron, which is more difficult to obtain than copper. This gives them an avenue for war-driven expansion if needed.

Low Priority:
Goths: Gives really nothing we're looking for except some influence. The gothic cavalry has the potential to have the highest combat strength classical era unit by fighting in enemy districts(29+3), however requires a massive 2(!!!) iron, which can not be procured consistently this early in the game.
Aksumites: Money focused culture, no bonuses to industry/influence/stability. Trait scales terribly. The Shotelai I think is underrated though, which saves the Aksumites from being lower on the list.
Carthaginians: Bad/niche emblematic trait(only useful if you have lots of money, which is unlikely at this point), and an emblematic quarter that is used as a port, terrible on a pangea map. War Elephants also are likely to be bad for their cost, as despite being the strongest classical era unit, the AI will probably be ahead and thus the elephant trample ability will unlikely trigger.

Wonders
1. A weak recommendation for Mausoleum at Halicarnassus. The rest are not worth building period.

General Guidelines
1. Leave cities on Growth. You can help new cities grow by creating cheap units in a high population city and disbanding them in the newer cities. If you've prioritized food during the ancient era, this should be done.
2. Again, continue to expand. You should not be cornered at this point, especially if you're playing on pangea. If you aren't playing pangea and are cornered, consider making a port and seeing if there are islands to settle. When expanding start prioritizing industry over food. Keep a look out for relevant strategic resources.
3. The way you handle diplomacy in general is the same here, look for trade deals, avoid war. Prioritize trade deals that give flat bonus to industry. One caveat is that if you've successfully locked out a passive culture from expanding, do not sign an open borders treaty. You want to keep them small.
4. If you've gotten access to horses at this point consider recalling and disbanding all your scouts and replacing them with horsemen. Horsemen set on autopilot at this point in the game can still yield a lot of resources.
5. In general you should avoid building military units at this stage unless you have an aggressive AI as a neighbor.
6. If war is declared on you at this stage, build palisades ASAP. A single palisade is worth more than any single unit at this stage and costs only 200 industry. In comparison a Praetorian Guard costs 180. Build enough units to survive, but do not try to take enemy territory. The way war works in this game is that the attacker will constantly lose war support every turn unless they win battles/hold enemy territory. Just outlasting them is enough to net you a win.
7. If you meet a minor/neutral culture(Independent People), feel free to spend money to start the process of assimilating them into your empire. Avoid spending influence on this pursuit.
8. Stars should be easier to come by at this stage. Again, I would not transcend to a new culture until my affinity stars have reached tier 2, preferably tier 3. The exception here being expansionist stars, which I rarely get further than tier 1. Avoid transcending until around 10-12 stars have been earned. You'll likely still be in the bottom third in terms of fame by the end of this era, which is okay.

Cultures
Again, at this point you're looking for industry/influence/stability, and food if you didn't manage to secure any during the ancient era. Science is now tied with food in terms of priority. The reason why is because a lot of the technologies in this era yield very real benefits for expansion/war, look specifically for the ones that give +1 to city cap. Money is still the worst of the FIMS. You are looking to be aggressive to keep the high fame cultures in check.

High Priority:
Khmer: Fantastic trait, emblematic quarter, and has one of the strongest emblematic units of this era(requires 2 Iron/Copper though). Hands down the best choice unless stability starved due to lack of trade, or playing an island map. but even so in the top 3 easily.
Franks: Mediocre trait, very good emblematic quarter(science/influence/religion), and quite possibly the best medieval era unit, the Franci Milites, when used correctly. The Franci Milites has a base strength of 39, but can get a gigantic +6 when charging, which can easily be triggered consistently when not fighting in a choke point. For comparison, a strength of 45(39+6) is comparable to several of the emblematic units during the Early Modern Era, such as the Rocket Cart(45), the Conquistadores(43), and the Janissaries(44).
Aztecs: My favorite back up choice if the game plays out in such a manner that I have few luxury resources/trades and no access to strategic resources. Their combat unit requires no strategic resources, they have arguably the best trait of this era(+2 land movement, -20% unit industry cost), and their emblematic quarter gives some influence/stability to boot. Really the only thing that's missing is industry.

Medium Priority:
English: My second favorite back up culture of choice if the game develops in such a manner that I lack luxury resources. A strong trait(though admittedly scales rather poorly), often generating 28-35 food per a turn per a city by the end of this era, a strong emblematic unit(borderline overpowered if terrain permits abusability), and a lackluster emblematic quarter. Of note, the English are the only agrarian culture for the Medieval era. Because agrarian stars tend to be the easiest to accumulate, this often leads to a quicker transcendence.
Teutons: Their trait is actually deceptively good, in that even though the Money and Science resources are not really what you're looking for, if you've prioritized food early on, your population total between all your cities will be in the triple digits by the end of this era, making it so that at minimum you're getting +100 money and science per a turn from this trait. The issue is that the teutonic knights can often times have difficulty triggering their Proselyte bonus(+3 against enemies with different State Religion). The thing is that if you've been following this guide, you're likely trading with a lot of people, since the Teutons generate a lot of faith, your Religion Pressure/Influence will be very high. This means neighbors/trading partners, will all often times be followers of your state religion.
Ghanaians: The better of the two gold-centered cultures during the medieval era, especially if you've been following this guide and prioritizing trade. The flat bonus per number of access to resources is just much better this early in the game. The emblematic unit is niche/mediocre.

Low Priority:
Mongols: Basically the Hun without the +2 to cavalry trait. If you've chosen the Hun prior, perhaps move the Mongols up a few ranks(I've never been able to pick this combination). The actual Ransacking bonus is largely only useful if you aren't strong enough to overcome the enemy in a siege at this point, as the goal here is to prevent the high fame cultures from winning, and ransacking alone isn't enough to do that. The actual Mongol Horde emblematic unit has the potential to just run over enemies if they have no anti cavalry, however they have low base strength and because of the way combat works in this game, where even if you outnumber the enemy 5:1, it's easy to be in situations where each of your attacks only deal 7 damage while you're taking 35.
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
At this point I would seriously consider transcending as the same culture for the 10% fame bonus rather than using any of the below
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Umayyads: A science culture that has a bad trait. On a good run, 3 alliances at this juncture would be considered good, meaning if it goes well, you're looking at a +15% bonus to science(+5% science per alliance on all cities). Since we haven't been prioritizing science, our base amount of science is low making the % scaling worthless. The Haras is weak for its cost, as the enforcer ability tends to not have an appreciable effect on Humankind Difficulty, as the AI gets a gigantic +60 stability bonus.
Byzantines: A gold centered culture that probably has the worst gold-related trait for the same reasons as the Umayyads. It should be noted that their Varangian Guards have the highest base damage in the game for this era, however require 2 Iron, which is not a given.
Norsemen: A culture designed for naval dominance will do poorly on pangea maps.

Wonders
1. Forbidden City. The way war works this game makes War Support incredibly useful - and now is the time whereby war will be the most common.
2. Angkor Wat if you've chosen to engage with the religion mechanic, otherwise ignore.
3. The other two are probably not worth building.

General Guidelines
1. Get the Professional Soldier civic(+1 to combat strength of all units). This combined with skew on to the homeland axis should yield +2-3 combat strength to all units, enough to offset the AI +2 bonus. Once this is accomplished, war becomes a realistic option under most circumstances.
2. Build up an army of your unit of choice and go to war. Targets whom have high fame or hold resources you need but refuse to trade should be prioritized. It is okay to leave targets that are difficult to access alone at this stage, but work towards carving a path to them. You NEED to go to war with high fame targets to give yourself time to catch up.
3. Technologies which yield +1 to city should be prioritized, if not outright beelined, if your current city count is 2+Cap or more(5/3, 7/5, ect...) as at this point culture penalties start to become significant. Also be on the look out for the technologies that unlock your emblematic unit.
4. Cogs are unlocked at this era with Sea Faring Mastery. If you have access to a port, consider making one early to auto-explore the ocean, especially if the map has islands. Cogs will occasionally be able to sail across to entire new continents by hopping from island to island, which can be useful if the New World option is on.
5. In terms of diplomacy, start seeing if you can ally with other cultures that have low fame, or one of your neighbors if you are surrounded. This can help prevent you from fighting multiple fronts. Usually by the end of this era you can secure at least one.
6. If you have enough cash, and are close to unlocking an emblematic unit, consider stock piling the precursor unit of the emblematic unit so you can upgrade all of them once the research finishes. This sometimes yields a powerspike that the AI will not have enough time to react to.
7. Spam Hamlets. If you've been following this guide your population should be large enough to take advantage of the additional specialist slots in most of your cities.
8. Again, do not transcend until you've gotten your two affinity stars, aim for 11-13 stars before transcending. If you've won a few wars you should be in the middle of the pack in terms of fame by the end of this era.

Cultures
Industry/influence/science are priority. Independent people are probably on the decline by now meaning that gold can no longer be used to expand via patronage, making influence even more valuable. Money follows in priority, as by now you're probably fielding enough units that unit upkeep/upgrades can bankrupt you. Food is the worst of the FIMS now, as the cities you'll be conquering should have sufficiently high populations. Enough luxury resources should have been secured by now that stability is a non-issue. The religion race tends to end in this era, most of the tier 4 tenets will be taken around this time. Your number one priority is to be aggressive to keep the high fame cultures in check.

High Priority:
Mughals: As the only industry bonus culture, the Mughals secure their place at/near the top with ease. Their emblematic unit is the strongest of this era, however are expensive and require 2 saltpetre, which is not a given.
Edo Japan: Beyond being the best influence producer of the era(carried solely by tier trait - the emblematic quarter is quite bad), I feel like the Naginata Samurai are undervalued. The Samurai are the only emblematic anti-cavalry unit of this era and unlock very early(Centralized Power, 1st column of Early Modern Era Tech), meaning they will be available when the AI are still using medieval era troops, the most dangerous being cavalry units(Teutonic Knights, Meharists, Franci Milites, ect...). With good positioning you can often stomp full stacks of 7 knights with 3 samurai, it's nuts. Move Edo Japan down a few notches though if the AI have no such units.
Ming: Another influence juggernaut, but not quite as consistent as Edo Japan if you've been prioritizing food early on as suggested. If you're population starved for whatever reason, put the Ming above Japan. Their Emblematic unit is very good, remaining relevant well into industrial era but requires a monstrous(3!!!) amount of saltpetre to access. Being able to build these while you are still in the Early Modern Era is not a given.

Medium Priority:
Spanish: Phenomenal trait, possibly the best in this era; +3 combat strength when starting turn in non-allied territory can be reliably triggered when you're being aggressive(which you should be). The issue is that the emblematic quarter is pretty useless at this stage. The Conquistadores are slightly weaker compared to their counterparts in exchange for the El Dorado trait(Generates Money from winning battles/ransacking), which is great if you're fighting weaker cultures but terrible otherwise.
Joseon: The best/only science producer of the era, even gives a bit of influence to boot. Would be higher on this list except its emblematic unit is naval, which is worthless on pangea maps - a terrible detriment when you're trying to be aggressive.
Ottomans: Solid emblematic quarter, solid emblematic unit, the primary issue being the trait. Realistically their trait(+3 strength/-50% cost to Heavy Weapon units) will only effect 2 units, the mortar and howitzer. Heavy units produced after the howitzer are rarely used, as the last two eras functionally do not exist in the game's current pacing. The mortar has a base strength of 40, becoming 43 with the trait bonus. The Janissary has a strength of 44 and has a better upgrade path, meaning 4/5 times you'll prefer building Janissaries over mortars(the 1/5 time being when -50% cost is significant/Indirect Shatter trait is valuable) - so realistically this trait only has an impact on the howitzer. It's just not that great.
Poles: Probably has the best Emblematic unit of this era, can be consistently built, the charge trait can be reliably triggered on maps with flat terrain The issue is the rest is pretty bad. Fortifications are not useful this late in the game as the goal is to be aggressive, while stability should also be solved by now.
Venetians: Solid trait if you've got access to a ports/trade routes(can be reliably done this late in the game), also have a great emblematic quarter that gives plenty of influence. They are this far down the list because similar to Joseon, their emblematic unit is naval.

Low Priority:
Dutch: Gold is useful now, but unlike the Venetians their emblematic quarter scales off of adjacent ports, terrible for pangea maps. Also their emblematic unit is naval. Bleh.
Haudenosaunee: Food is low priority, making the trait and quarter bad. The Rotiskenrakehte is interesting because of the Stealth trait. I have not had the opportunity to thoroughly test this out, but it feels like it could be very good defensively. The issue is that stealth is useless when sieging, which you should be doing a lot of. Would probably prefer transcending the same culture.

Wonders
1. Topkapi Palace. You'll want additional industry to help earn fame with the national projects later on.
2. Machu Picchu if you've managed to secure multiple cultures with traits/quarters that scale with population.
3. Rest are generally not worth building.

General Guidelines
1. Once you're done building your army, consider swapping your cities to balanced or even technology subsidies if you've gotten some science cultures. At the moment you're likely behind in technology.
2. If you've snagged a culture that has given bonus to religious production, you should be hitting tier 4 tenets by now. The Meditate Often tenet gives a gigantic +2 strength to all followers. It sounds OP, but is tempered by the fact that this bonus is applied to all followers and not just you. If another culture snags it, consider becoming a follower of their religion(religions tab, left side panel).
3. Secure a path towards the high fame targets by any means necessary. If they happened to spawn at the opposite side of the pangea land mass, consider using naval units. Naval units that can travel safely across deep waters will be available at this point. If the option is turned on you can wrap around the map via a naval route.
4. In a similar vein, because naval units can cross deep waters now, if you find yourself locked in for whatever reason, now is also a great time to expand to faraway islands/the New World continent.
5. It is common for the number of cities you accrue due to war to begin exceeding your city cap by a large amount at this point, even with the relevant technology bonuses. Consider vassalizing opponents or only taking outposts. Also, if the AI has built many cities with few territories, you can consolidate them into one big city after war by Absorbing them(unlocked via Military Architecture, which should be available to you at this point). If absorbing becomes too expensive, raze the cities and replace them with outposts, which should be quick when placed on ruins. Attaching these new outposts should be much cheaper than merging the cities.
6. Get your two affinity stars/12-14+ stars before transcending. If you've been winning wars you should be in the upper half of fame by the end of this era. If you're behind by more than 4k fame at this point and have no easy access/are unable to conquer the top fame cultures you're likely to lose.

Cultures
Industry/science are priority, followed closely by influence(Unless you're not near your city cap/can easily expand - then prioritize influence), Money third, then finally Food. Again at this point luxury/religion should be non-factors. You're looking to maximize fame at this point. These last two eras will go by really fast. The later Industrial Era combat units may not even see any play. The game is typically decided about half way through this era.

High Priority:
French: Absolutely monstrous science potential with their emblematic quarter, and a fantastic emblematic unit(+9!!! charge) that unlocks early enough to see significant use. The trait is mediocre, but regardless the French definitely should be one of your top picks with this strategy.
Germans: If the French are monsters at science production, the Germans are monsters at Industry - in fact if it were not for the fact that they have a naval emblematic unit, I would place the Germans above the French.
Austro-Hungarians: The best Influence producing culture in this era. Unfortunately, the Evidenzbureau Agents unlock a bit too late to see much use.

Medium Priority:
Siamese: Very solid Gold/Industry production. Less industry than the Germans, however, the gold production is high enough that one can easily hit tier 3 merchant stars routinely with the Siamese. The issue here is that their emblematic unit unlocks incredibly late and has a very selective upgrade path(can be upgraded into by 2 other emblematic units), thus will unlikely see much play.
Persians: The raw industry bonus of the quarter is essentially negligible, however their trait is quite good. The -25% cost of Shared Projects will make the National Projects/Wonder construction you'll be doing go that much faster. The cherry on top is that their emblematic unit unlocks at the very start of the era, making it likely that they'll see significant play.
Italians: Essentially worthless trait, but a very solid emblematic quarter that will produce a lot of influence and the Alpini unlocks relatively early and has an easy upgrade path.

Low Priority:
British: Similar to the Italians in that the trait is bad, the emblematic quarter is good(produces gold instead of influence), and good emblematic unit(in fact, the Redcoat is probably better than the Alpini). The reason why the British are lower is just simply because influence still tends to be more valuable than gold at this point.
Russians: If you're still making a lot of units, Russians should be higher on the list - the issue is that by this point, you're largely upgrading your existing armies rather than building new units making their trait pretty bad. Their emblematic quarter is downright useless as well. The thing keeping them from the bottom of the list is that the Cossack unlocks early and has an easy upgrade path.
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At this point I would seriously consider transcending as the same culture for the 10% fame bonus rather than using any of the below
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Zulu: Being defensive at this point is going to lose you the game, unless you're really far ahead - and that's about the only thing the Zulu are good at.
Mexicans: At the very least the Zulu can be useable if you're ahead - the Mexicans are pretty much never useable this late in the game using this strategy.

Wonders
You'll want to be building all of them for the 100 fame. I would prioritize them in this order:
1. Eiffel Tower
2. Big Ben
3. Statue of Liberty

General Guidelines
1. Technologies will be researched at a very fast pace, frequently within 2-4 turns per technology, make sure you keep your units upgraded. Having Shared Logistics with your allies will make this easier.
2. If you need to farm some quick stars, do not be afraid to break some treaties/alliances at this point to earn Militarist/Expansionist stars. You can do the same by liberating your own cities then attacking them.
3. Start looking to complete the Competitive Deeds at this point. Some that are consistently easy to get and are still available usually are:
-Build a Symposium
-Circumnavigate the World
-Construct a railway line between 2 cities
4. The game should essentially be decided at the end of this era. If you're more than 3k fame behind, it can be difficult to catch up. I would suggest staying in this era until you're within striking distance (1.5k fame) of the number 1 spot.

Cultures
Priority at this point determines on how you wish to trigger the ending. I usually trigger mine through science/mars project, so I usually prioritize science. The reason for this is because the end game science techs all give large chunks of fame. Money tends to be bad here as national projects cannot be rushed. If you're sufficiently ahead however and can win by domination, feel free to do that. On standard speed contemporary Era units essentially never see play. Even on slower settings they some times do not - thus this list does not consider them during ranking.

High Priority:
Swedes: Just absolutely absurd science production. Often times I'm researching more than 1 technology per a turn when I spam their Research Institute(standard speed). Easy to set-up, as they scale based on the number of districts the city owns. This means even cities with terrible layouts for adjacency bonuses(almost all of the AI developed territories) can reasonably take advantage of them. Secures technology related fame. Often saves me 15+ turns of boring game play when I'm ahead.
Japanese: If you're in a situation whereby the fame race is very tight and you need to complete wonders/national projects to win, I would go with the Japanese. Still a huge amount of science(with the -20% technology cost trait to boot), along with a large amount of industry to help you finish those projects.
Soviets: Only here for their trait. The district is actually pretty mediocre - still, If you're attempting to end the game by military domination there's no better pick. +3 combat strength to all units is fantastic.

Medium Priority:
Turks: The most situational science generator of the bunch. The value of their emblematic quarter is contentious. After much discussion, I believe that yes, they have the highest potential(cities with 50-60+ population and good science adjacencies can reach 1.5k+ science/territory consistently). The issue is that they will not be anywhere near that potential for cities with smaller populations/unoptimized districts(which is always the case for AI built territories), ie. most cities. The trait only generates food and is thus worthless. Are actually technically considered a culture with an agrarian affinity, so do not have access to the Collective Minds affinity action, which is frequently worth several hundred science/city.
Australians: Offers a tremendous amount of Industry - the reasoning here is similar to the Japanese, the late game fame generating projects are all largely gated by industry. They do not however generate any science.

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At this point I would seriously consider transcending as the same culture for the 10% fame bonus rather than using any of the below
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Low Priority:
Egyptians: A great influence generator, meaning that you'll be able to get the aesthete stars, which tend to be difficult to earn. At best this means +50/100/150 or 300 fame, worth a single late game tech.
Americans: A worse influence generator than the Egyptians.
Indians: A worse influence generator than the Americans.
Chinese: Money generator, and not even a particularly good one at that.
Brazilians: Food generator - a very good one actually. Unfortunately food generation is useless at this point.

Wonders
You want all of them for the 100 Fame bonus they each provide. I would prioritize them:
1. Sydney Opera House(Unless stability is an issue then this is last place)
2. Christ the Redeemer
3. Empire State Building

General Guidelines
1. If you have access to it(and are ahead), turn on the Collective Minds affinity action on your cities to save yourself some time.
2. Ensure you've built all available Luxury Manufacturers in all available cities. Each one is worth 50 fame, and it is not uncommon to have half a dozen or so this late in the game.

If the race is tight, you can get some extra fame by doing the following:
1. End game Technologies(5x300 = 1500 total)
2. National Projects, 3 sets(Nuclear Weapons test, Lunar Landing, and Planetary Observation
Satellite), each give a possible total of 300(3X300 = 900 total)
3. Competitive Deeds, most commonly Own a Nuclear Weapon(50), Explore the Entire Map(150)
and Complete a National Project(50)
Total = 2,650 Fame

Of course, do not trigger the ending until you have the most fame.

As stated before, this guide was built on player experiences based on an early release build of the game. I anticipate that significant changes will take place during the game's lifespan and will attempt to update the guide. This guide is still an early draft - I am still quite willing to change my view on things. This is a relatively long read, I appreciate those who've been willing to hear what I have to say. Thank you.