Central Los Santos Is a Industrial and financial region bordered by Vinewood, Western Los Santos, Southern Los Santos, and Eastern Los Santos.

Downtown LS:

The district is the home of most of the city's skyscrapers and corporate buildings, including the large Maze Bank Tower, the tallest skyscraper in the city and the state. The headquarters of both the International Affairs Agency and the Federal Investigation Bureau are also present here. The western half of the district acts as the main financial center (Pillbox Hill), while the eastern side is home to smaller businesses and residential areas (Mission Row and Textile City).

The district is bordered by Olympic Freeway at south, La Puerta Freeway at west, Del Perro Freeway at north and Los Santos Storm Drain at east. Because of that the district is excellent communicated with the rest of the city. Also, Strawberry Avenue ends at the Los Santos Freeway. There are two Los Santos Transit stations (one closed) and several buses. However, heavy traffic is common all day and all night.

La Mesa:
La Mesa is bordered by Mirror Park and East Vinewood to the north, Textile City, Mission Row, Strawberry, and Rancho to the west, Cypress Flats to the south, and Murrieta Heights and El Burro Heights to the east.

Like other neighbourhoods in East Los Santos, La Mesa is primarily an industrial neighbourhood. However, unlike other areas, La Mesa seems to be more developed, possibly as a result of gentrification from nearby Mirror Park. There also seems to be less gang activity as well. La Mesa is still an economically deprived neighbourhood with abandoned factories and warehouses. However, the presence of a Los Santos Customs indicates it is slowly growing out of poverty.

La Mesa mostly consists of a main road that passes straight through it, with a few smaller streets here and there. The main road is north-south, so it can either lead up towards Mirror Park or down to Cypress Flats. La Mesa is located right next to the Los Santos Storm Drain. The other roads in La Mesa can lead to the storm drain or to the outskirts of the city.

Pillbox Hill:
Pillbox Hill borders Strawberry and Chamberlain Hills to the south, Little Seoul to the west, Burton and Alta to the north and Textile City and Legion Square to the east.

Pillbox Hill is Los Santos' commercial and financial center. The district contains most of the city's major skyscrapers and associated financial institutions. Pillbox Hill is home to the main headquarters of companies like Maze Bank, Schlongberg Sachs, Union Depository, Lombank, Tinkle, GoPostal or Penris, among others. It occupies approximately the western half of Downtown Los Santos.

Mission Row:
It borders Textile City to the north, Strawberry to the south, Legion Square and Pillbox Hill to the west, and La Mesa to the east. It is based on the real-life neighborhood of Skid Row, in Los Angeles.

Mission Row is relatively small and only has a few number of streets. Just like Textile City to the north, Mission Row holds a number of businesses and stores, especially jewellery shops despite the fact that it contains a considerable population of homeless people like its real-life counterpart, Skid Row, which has one of the largest populations of homeless people in the United States. The name "Mission Row" is most likely a reference to the missions that provide food and basic assistance to the poor in Skid Row.

Its streets and sidewalks are lined with boxes, tents, and shopping carts, which contrast with the nearby high-end hotels and office buildings of Pillbox Hill. The few high-end hotels located in this neighborhood show a large difference between the denizens of Mission Row and its buildings. Occasionally, there will be a mugger trying to rob a pedestrian. Police officers can often be seen patrolling the streets in pairs or talking to pedestrians.

Textile City:
This neighborhood is known for its factory outlets, wholesale stores and retail shops. There are many clothing stores lined up along the streets of Textile City. It was formerly an industrial area, as indicated by the reused factories that turn into makeshift stories. Just like neighboring East Los Santos, the effects of gentrification and tourism caused a new buildup of commerce and business in the neighborhood. A decommissioned railroad is nearby, along with a few warehouses that are still serving their original purposes.

Many shoppers can be seen frequenting here during daytime. The famous Simmet Alley is a crowded, bustling marketplace full of buyers and sellers. Most of the stores in Textile City are either clothing and fabric stores or restaurants. It is also home to two theatres, Foxy's Theater, and the Ten Cent Theater, the latter of which is a purchasable property in story mode.

Textile City is bordered by Downtown Los Santos in the north, La Mesa in the east, Pillbox Hill in the west, and Mission Row in the south. It is one of the smallest districts in San Andreas, true to the real life Fashion District of Los Angeles, and covers just two blocks laterally and longitudinally. San Andreas Avenue denotes the border between Textile City and Mission Row.