Capitol Policeman John Cale has just been denied his dream job with the Secret Service protecting President James Sawyer. Not wanting to let down his little girl with the news, he takes her on a tour of the White House, when the complex is overtaken by a heavily armed paramilitary group. Now, with the nation's government falling into chaos and time running out, it's up to Cale to save the president, his daughter, and the country.

A fearless, globe-trotting, terrorist-battling secret agent has his life turned upside down when he discovers his wife might be having an affair with a used car salesman while terrorists smuggle nuclear war heads into the United States.

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.