The Enchanted cave might seem like a difficult game to get through without grinding some levels, however it is possible to beat the game in only one run, and without a great deal of grinding. The primary reason for this is because of how good the combat skill tree is early on in the game, and even into the end-game. The Enchanted cave’s battle system heavily favors the defense stat over every other.
In general, the stats that should be prioritized in the game are Defense, then Attack, then Potion efficiency, then Magic, and finally Potion Duration. The heal skill can be found early on the magic tree and should be gotten as soon as you acquire any form of mana regen. As has been mentioned in many other guides, Mana Regen is one of the most valuable skills as its regeneration rate is multiplied by 2 + (your Magic/(~18)) when using Heal. Late game, 1 mana regen can be equivalent to 5-7 Health Regen, often allowing you to clear mobs indefinitely. However, some of the most underrated skills in the game are Defense boosts and Elemental Resists. Proper Elemental Resist equipment will allow you to clear many floors at a time without much trouble. (Proper Elemental Resists can often allow you to take 0 damage from magic-based mobs)
As such, in order to progress through the game in only 1 run, every level-up should raise the Defense stat, and the early skill points should all be spent on rushing Defense stats in the combat tree, and then the Attack Stat. You should start hoarding potions after around floor 20, save mana for forges, and then enchant only your best equipment (that you will use for at least 5 floors or more) with the top crafting components.
Also, it is important to try and save as much money as possible early on. Buying crafting components that have mana or health restore can save money compared to straight buying the respective store- health and mana potions. (You should be saving those potions for bosses)

The first 20 floors are the easiest that can be cleared straightforwardly. These floors are the perfect floors to grind. At the starting shop, you want to spend your gold to boost your defense. Buy a plank shield, a straw hat, and some gloves for the maximum defense buff. You probably also want to buy equippable items at floors 10 and 20 in order to boost your stats.
Through these floors, try to fight as many mobs as possible that will do less than 20 damage to you per fight. It may be worth it to go through stronger mobs in order to reach an artifact (in a red chest), however, I would say that taking over 50 damage just for 1 chest is risky. You can check how much the damage the mobs will do to you per attack by calculating the difference between their attack and your defense (and resists). Resists are not too important in early levels. Finally, try to avoid stronger mobs as much as possible.
The small brown boxes in these early levels are not very useful, however the Viscous gloop crafting item (dropped by purple slimes) is very useful for the first few levels. The Fungus helm gives 4 mana regen and is one of the best items early (Artifact in red chests floors 17-26) The run will become MUCH easier if you are able to pick this artifact up, so try your hardest to find one. An important note is that every green chest after the first one will drop a potion. The potions on these floors dropped by green chests will be 75 health potions and 10 mana potions. It is easily worth it to take a 75 damage in order to agressively reach these potions. You get gold, xp, and your health back in these cases.

The shops on floors 30 and 40 do not sell any items. Only potions and crafting components. Stocking up on items on floor 20 can help aid you through these increasingly difficult floors. In these stores, you can buy mana pots and aggressively enchant almost all of your good equipment by continually refilling mana. Some of the more valuable item skills will be mana regen, health regen, defense, and earth resist. These stats can help you grind a bit more safely on these floors as well as preventing you from taking too much damage as you try to reach red or green chests, or the stairs. In these cases, turtle shells, geodes, cabbages, and blue jungle berries are some of the most valuable crafting components.
For the next 20 floors, try to fight as many mobs as possible that will give you at least 1hp – 1.5xp ratio. (meaning that for every point damage you take during a kill, you will get 1.5 times that much xp after you kill the mob) there will be mobs on these floors that you can kill without taking any damage, and there will also be mobs that will deal a great deal of damage to you. For every strong mob you go out of your way to fight, you can probably fight a weaker mob to get some regen and heal back up. This strategy will allow you to grind more mobs than before, giving you the opportunity to not only clear weak mobs for xp, but stronger ones as well.
Try to get as many crafting components as you can that have ice resistance on them. Stages 40-60 are heavily littered with enemies that have ice attack, so stocking up on ice resistance now will help you a great deal later on. A few crafting components with wind resistance on them as they will be useful later on. A good gold stock will help you buy crafting components at every store you get to, allowing you to enchant more of your items, sometimes even your discard-able equipment. There will be some earth attack and dark attack monsters on floors 20-40, but their dark and earth attacks are low enough that you shouldn’t need to worry too much about adjusting your equipment to resist them.
Starting from floors 30 and onwards, you should begin to stock up on magic pickaxes as they will greatly aid you in getting through floors 80-100.

These are some of the easier floors if you are able to spec your equipment properly. As mentioned before, ice resistance is a crucial stat for these floors. With enough ice resistance built up, many of the monsters on floor 40-60 will do 0 damage to you, meaning unlimited grinding. These floors should be pretty simple to beat. Just stack up your defense and ice resistance and the game should do the rest for you. Even the yeti boss becomes a joke when you have enough defense, as it would continuously go through animation upon animation, bringing its arm down upon you over and over to do only a pitiful 0 damage.

Grinding the mimics that appear later are also useful as they will often drop magic pickaxes after they are defeated. Important note that there is no shop on floor 50, so the only buy you will get will be on floor 60. Try to hold on to crafting components that have light and wind resistance as you will need them for the next 20 floors. Also, from floors 50 onwards, you should use every level up should and rainbow gem to increase your attack stat.

These few floors become the point where the defense stat will no longer protect you from all forms of damage. Managing your equipment and stats to get a good mix of attack, defense, and elemental resistances will allow you to optimally clear these floors. You should start putting different sets of equipment with different stats/elemental resists to account for the many different types of enemies you will be facing. It might be easier to keybind your equipment to the number hotkeys so that you can quickly swap between them before a fight. Overall, light and wind resist will be the most useful on floors 60-80, but fire and earth resist will also protect you from certain enemies. (remember to hold-click on an enemy to see their elemental attack and resists!) Enchanting your equipment to enhance their resistances should be easy at this point as you should have acquired and kept several items with mana regen on them.
It is no longer necessary to grind from floor 60 onwards as every level up will only provide you with very minimal increases in your stats. Thus, you shouldn’t take any fights that would damage you too much, and even artifact chests will not be worth it if you need to take 250 or more unhealable damage to get to them (damage that you don’t heal back after regens). Green chests that hold potions become extremely valuable as they will contain either medium or large sized potions, and with potion efficiency, their effectiveness becomes incredible. (1 medium potion can heal you from 200-300 hp). It is easily worth it to take 200 points of unhealable damage just to get to a green chest.
The real challenge lies on floor 80: The necromancer. This boss will attack you with magic spells, meaning that on top of his high base 330 attack, he will deal damage to you through every possible elemental attack. It will be important that right before you fight the necromancer, you should craft some stat-giving potions for these stats (in this order): defense, attack, bleed, decimate, crit chance, any elemental resist, dodge chance. These potions will be used for this 1 fight to greatly reduce the damage you will take (and the amount of active healing potions you will need to use), and save you some time and money in the long run.
Try to save up your fire, dark, and light resistance components.

These are by far the hardest floors in the game. There is a heavy concentration of monsters with fire and dark attack, and the final boss on floor 100 has the same. The monsters here have extremely high attack, defense, and hp stats. If you’ve been stocking up on potions and magic pickaxes, these floors should not be too hard for you. Try to avoid as many fights with strong enemies as possible, now using your magic pickaxes to go around fights you cannot take. You may be able to take some fights from floors 80-90, but definitely avoid as many as possible from 90 and onwards.
There will also be some normal items to get and normal chests to open from floor 85 onwards, from the berserk blade and demonic shield to the royal boots. The idea is to get as much equipment that has high defense and fire and dark resistances while maintaining a weapon with high offensive capability, all for the final boss. If there is an easy path to a chest, you should try to take it. You must reach the final boss with a good weapon, good enchantments (gives some of your equipment decimate/bleed for the final boss, maybe onto some of your spare rings ; if you run out of bleed/decimate, then attack, defense, dark, and fire resist become your best options), heavy defense, high fire and dark resistances, and plenty of potions (probably a stock the equivalent to 30 medium potions). You should also keep enough of your crafting components for the final boss to make yourself stat potions of these types in this order: bleed, decimate, dark resists, fire resist, defense, attack, crit chance, dodge chance. You should try to have at least one component to provide a buff for each of these stats.
Hopefully you’ll also be able to complete the game without ever using the escape wings!!!
(or at least kill the final boss =P)