The second game in the series; it follows Jack, the same survivor from the first game. He is breathing a sigh of relief in the rescue helicopter when one of his group members turns out to be infected. The resulting chaos causes the helicopter to crash, with Jack as the only survivor.

This game illustrates his trek towards Union City, where news of a final evacuation is said to be taking place in 40 days. It possesses the same mechanics as The Last Stand, except the player must now travel across a map through different towns in order to reach safety, and must gather weapons, survivors, and supplies along the way.