The game?s diverse operating environment includes a unique and exciting game mode in which three different parties battle each other: zombies and bio-organic weapons (Bio-Organic Weapon, or BOW) shuffle the pack as players battle government special forces. Zombie troops add to the battles the unpredictability inherent in Resident Evil?s perverted world. The game thus renews the genre by breaking the conventions of traditional third-person shooting games.

It is September 2008 and a deadly T-virus epidemic has just broken out in Raccoon City. The Umbrella company wants to conceal what happened and sends its special forces to the city to destroy the evidence of its involvement. The government, on the other hand, has quarantined the city and sent its own troops to find out the origin of the epidemic. New local police officer Leon S. Kennedy and Claire Redfield are caught in a crossfire between the parties.

Players play USbrella security forces USS soldiers and battle all parties fighting in Raccoon City. The player gets to choose from six characters, each with their own specialty, including female researcher Four-Eyes, who is able to manipulate the T-virus and control BOWs terrorizing the city streets, and weapon expert Lupo, who serves as the leader of the USS team.