Leon S. Kennedy and Claire Redfield must battle a rogue warrior seeking revenge after unleashing the deadly G-Virus, whilst a mutated monster goes on a rampage.

U.S. federal agent Leon S. Kennedy sneaks into the "East Slavic Republic" to verify rumors that Bio-Organic Weapons (BOWs) are being used in the country's civil war, which the U.S. and Russia are making preparations to jointly intervene in. Right after his infiltration, the U.S. government orders him to leave immediately. Determined to uncover the truth, Leon ignores the order and enters the battlefield to end the chain of tragedies caused by the BOWs.

BSAA Chris Redfield enlists the help of government agent Leon S. Kennedy and Professor Rebecca Chambers from Alexander Institute of Biotechnology to stop a death merchant with a vengeance from spreading a deadly virus in New York.

In San Francisco, Jill Valentine is dealing with a zombie outbreak and a new T-Virus, Leon Kennedy is on the trail of a kidnapped DARPA scientist, and Claire Redfield is investigating a monstrous fish that is killing whales in the bay. Joined by Chris Redfield and Rebecca Chambers, they discover the trail of clues from their separate cases all converge on the same location, Alcatraz Island, where a new evil has taken residence and awaits their arrival.