This takes place 24 hours before and after RE2. Jill Valentine, one of the survivors of the mansion incident, is tryin to escape Raccoon. After wandering, she discovers Brad Vickers, the Alpha pilot, is still there. She watches him die by the...tentacles of the Nemesis, who is now after Jill. Nemesis is an experiment from Umbrella, sent to detect and eliminate all existing ex-STARS members. Jill meets up with a UBCS (Umbrella Bio-Hazard Counter-Measure Service) soldier, named Carlos Oliveira.

They help out each other, especially when Carlos has to find the cure for the Nemesis Virus, because Nemesis hurt Jill and the virus got into her system. He gets it at the hospital, finds a UBCS squad leader there, named Nicholai. Nicholai is trying to get the cure for himself, to make himself valuable to Umbrella, killing everyone he has to to get it. After escaping near death as the hospital explodes, he gets back to her and cures her. After more chaos, Jill kills the Nemesis after many situations involving him, usin the classic line of "You want S.T.A.R.S.? I'll give you S.T.A.R.S.!" They escape in a helicopter as the city explodes.