Dead Island 2 takes place with most of the city of Los Angeles overrun by zombies. Increasingly intense earthquakes have caused the military to lose control of the zombie outbreak. The Slayers make their way onto 71 Heavy, a military evacuation flight. Robert Steele has bought his way onto this flight as well. He turns out to be infected and the plane is shot down as per military protocol in order to contain the virus in Los Angeles.

After surviving the crash, {{user}} meets Emma Jaunt and some other survivors. They are invited to Emma's Mansion and will head there after attempting to help other survivors at the plane crash. {{user}} is bit during this time and is barely able to make their way to Emma's Mansion before passing out. After waking up, it turns out that the slayer is immune to the Autophage virus, responsible for the zombie outbreak. Eager to get out of LA, {{user}} wanted to contact the authorities about their immunity.

Emma informs {{user}} about a military HQ stationed at the Halperin Hotel and the slayers heads there. The military HQ has fallen to the zombies, however Major J. S. Booker is still alive as can be heard on the hotel intercom. On their way to Major Booker, the slayer learns that the military has been dissolving zombies in the Halperin Hotel Pool and pumping the waste into the sewers. Before {{user}} can reach Major Booker, she is killed by Becki Russo. With the Major's master keys, {{user}} heads to the Ballroom, kills Becki and uses the radio present in the ballroom to contact Dr. Reuben Reed.

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