A teenage rebel James “Jimmy” Hopkins, a difficult student with a disruptive background, is being dropped off at Bullworth Academy, a fictional New England boarding school.

Michael is a retired former bank robber in his early forties who lives with his dysfunctional family on the proceeds of his former life in the upper-class suburb of Rockford Hills. Trevor, his former partner in crime, lives alone in a trailer in the desert of Blaine County, where his reckless and psychopathic behaviours are fuelled by drug addiction. Franklin makes a living in Vespucci Beach as a repo man for an unscrupulous Armenian car dealership.

Toni Cipriani, having been forced into living abroad after killing a made man on the orders of Salvatore Leone, decides to return to Liberty City. Upon arrival Toni is greeted by Salvatore and a member of the Leone family, Vincenzo “Lucky Vinnie” Cilli, who rose to prominence during Toni’s absence.

In 1992, Carl “C.J.” Johnson returns to Los Santos after spending five years living in Liberty City when his brother Sean “Sweet” Johnson calls to inform him of their mother’s murder. Shortly after leaving the airport, Carl is intercepted by a group of corrupt LSPD C.R.A.S.H. officers led by Frank Tenpenny, with whom Carl has a history.

Tommy Vercetti, a loyal former member of the Forelli Family, has just been released in 1986, serving 15 years for killing 11 men in the Harwood District of Liberty City in early 1971, earning him the nickname The Harwood Butcher.

Vic Vance is a corporal in the U.S Army. He is a man who came from a poor family, with his brother suffering from asthma and another lazy brother, and he is trying to make money for his dysfunctional family. He just arrived in Vice City in 1984 and he is now stationed at Fort Baxter.

In 2003 in Carcer City, the story opens with a news anchor reporting on James Earl Cash, a death row prisoner recently executed by a lethal injection. In reality however, Cash awakens to hear a voice coming from an earpiece, revealing his lethal injection was only a sedative.