Frank West & his pupil,Vicky Chu investigates the destruction of Raccoon City. After they are taken by S.T.A.R.S.,Fontana & her men begun killing members to find Frank ever since the zombies attack the mall. Rebecca Chambers helped Frank & Vicky escape by taking them out. She tells them about a distress call going on.
Fontana hires Calder to hunt them down. Later,Frank,Vicky,& Rebecca found a dead man before being attacked by a mutated leech,sent by the Queen Leech. They manage to escape and begun making a discovery at the lab. They learned that the mutated leeches were created by the scientist & co-founder of Umbrella Corporation,James Marcus,who was assassinated by the order of the other co-founder,Oswell Spencer.
They are ambushed and captured by Calder & his men. They are suddenly attacked by the Queen Leech,who kills Fontana while Calder fled. The Queen Leech is reveal to be the re-animated James Marcus,who was brought back by the mutated leech.
Frank & the others escape and made their way to the train. The Queen Leech later transforms into a monster and attacks them. The Military launches the missle which destroys the bridge. The car that Frank & the Queen Leech are on dangles. Frank made his way up & shoot the hook,sending the monster and the fuel car crashing down. As they leave,They are both picked up by the S.T.A.R.S. Helicopter.
Mid-Credits:
Calder was found by Wesker,who tells him that he has a job for him.