The game is set in the United States following a cataclysmic event which caused destructive creatures to begin roaming the Earth. Players control Sam Porter Bridges, a courier tasked with delivering supplies to isolated colonies and reconnecting them via a wireless communications network. Alongside Reedus, the game features actors Mads Mikkelsen, Léa Seydoux, Margaret Qualley, Troy Baker, Tommie Earl Jenkins, and Lindsay Wagner, in addition to the likenesses of film directors Guillermo del Toro and Nicolas Winding Refn as supporting characters.