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.
One day, Naho Takamiya receives a letter written to herself from ten years in the future. As Naho reads on, the letter recites the exact events of the day, including the transfer of a new student into her class named Kakeru Naruse. The Naho from ten years later repeatedly states that she has many regrets, and she wants to fix these by making sure the Naho from the past can make the right decisions—especially regarding Kakeru. What's more shocking is that she discovers that ten years later, Kakeru will no longer be with them. Future Naho asks her to watch over him closely.
Andy, a Negator with the ability "Undead," has been long in search for someone with the ability to give him a 'real death.' Fuko Izumo brings misfortune to those around her due to her ability "Unluck." The two decide to join the Union, an organization which aims to control and protect the world from unidentified phenomena. The two uncover the mystery of the world as they search for the "greatest death ever."
