This game covers the events of Resident Evil 2 (1998), Resident Evil: Code: Veronica (2000), and a new event in South America ('Operation Javier') that was mentioned in a BSAA file.
It's learned that Rockfort Island where Resident Evil: Code: Veronica (2000) takes place is situated off the west coast of South America, and not Europe as originally thought (despite a file found in Resident Evil: Code: Veronica (2000) stating that it was "far south of the equator").
This is the only Resident Evil game where Claire Redfield and Ada Wong meet.
Chronologically, this marks the first appearance of Jake Krauser, an evil traitor who appeared in Resident Evil 4 (2005).
The 'Game of oblivion' segment of this game is more closely based on the original Dreamcast version of Resident Evil: Code: Veronica (2000), rather than the extended and wider released version, Resident Evil - Code: Veronica X, which became available in 2001. Like in the 2000 game, Albert Wesker only makes a very brief appearance at the end of the Game of Oblivion segment, whereas in Code: Veronica X, he had several physical confrontations with other characters. A major difference with either version of Code: Veronica is that Alfred challenges Claire and Steve to a game, by sending them through a kill house in the basement of his Military Training Center. The kill house appears in no version of the original game.