If the player fails the Running Dog mission while CJ's fat level is over 50%, Big Smoke will call CJ afterward. He tells CJ to go to the gym and lose some weight.

Pictures of characters from Grand Theft Auto III and Grand Theft Auto: Vice City are used on the playing cards in the Video Poker minigame.

On the Tiki Theater Xymposium building in Los Santos, close to Grove Street, there is a giant tiki idol resembling one of the collectible hidden packages from Grand Theft Auto: Vice City.

David Cross, the actor who voiced Zero in the game, said that he hated the mission "Supply Lines", which his character was in, because of how difficult it was and finding his voice accompanied with it to be annoying.

In an interview, Cross said, "It's the most annoying voice you could imagine, accompanying that," "I stopped, I tried to cheat, I could not listen to myself, it was so annoying," "So annoying. I hated it. And I couldn't fucking do it. The RC thing? ... It's impossible."

San Fierro was originally named "San Fiero". This can be seen on unused textures within the game's files.

A pedestrian in the game wears clothes that bear a striking resemblance to an outfit that Cuba Gooding Jr.'s character Tre wears in the film Boyz n the Hood, a film that heavily influenced the game.

There is a pedestrian that bears a resemblance to Tupac Shakur's character Bishop in the film "Juice". The film came out the same year that the game takes place in, 1992.

A pedestrian bears a striking resemblance to Sharon Stone's character Catherine Tramell in the film "Basic Instinct". The film came out the same year that the game takes place in, 1992.