Jill and Claire are the main characters, with Barry and Jake as secondary/side characters. At the beginning of the game, it's revealed that Jill is suffering from mental illness due to her ordeal with Wesker and from still "seeing" Wesker (in flashbacks/hallucinations) despite watching him die years ago. She is being treated at a psychiatric ward after being transferred from the BSAA facility where she was tested after RE5. However, Jill awakens in her cell from a nightmare involving both Weskers and finds the facility compromised. Jill escapes with Barry and Claire, who try to meet with her following her e-mail in Rev. 2..
Halfway through the game, Barry finds Natalia after she "mysteriously" runs off, then "Natalia" shows her true colors and stabs and kills Barry before shapeshifting back into another mutated form of her true self (Alex). Claire kills Natalex, then searches for Chris along with Jill (the 2 most important women in his life), who's eager to get back to him after RE5, only to run into more B.O.W.s along the way. They eventually cross paths with Jake, who's also been hunting B.O.W.s since RE6 when "something" captures Claire in the distraction. Jake and Jill go their separate ways, with Jake trying to find Chris and Jill searching for Claire.
In the separate campaigns, Jake is eventually captured by a silhouetted figure and the same group of henchmen from the opening cutscene of Rev. 2 after a B.O.W. boss fight while Jill is taunted by hallucinations of Wesker at various intervals leading up to the final chapter.
In a cutscene before the last level, Jake is seen in a glass test tube right beside Claire, where a silhouetted Alex speaks of Jake "finally getting to meet his true family." Jill eventually crosses and fights HUNK after freeing Claire, who is then unmasked as Jake (plot twist). A stunned Jill is then met with a familiar chorus of evil laughter when "Albert" appears, brought back to life through Alex's transferred consciousness after she reanimated his corpse with T-Phobos. Jill then injects herself with a syringe and destroys Albex, basically killing 2 birds with one stone, or rather, two Weskers with one stone, using a modified version of the P30 drug "he" spent years experimenting on her with that leaves her fully in control of her actions (via antibodies). The ultimate revenge, and irony.
