The gameplay focuses on brawls against large groups of zombies, using combinations of melee and ranged attacks along with thrown weapons to mow down zombies in spectacular ways. The game uses an extensive crafting system where players can create and customize their own weapons along with building many types of vehicles. Players get to explore Willamette which has changed a lot since his last visit, including the mall from the original Dead Rising transformed into the central Willamette Memorial Megaplex. The game offers many items to discover and collect such as weapon blueprints and hidden graffiti art to photograph. There are also side quests, hidden bosses known as Maniacs and additional investigations to pursue along with events to rescue survivors or destroy military equipment.
The game's save system is now more traditional based on checkpoints, rather than a limited amount of saves. The game still supports cooperative multiplayer, but now only for separate episodes where a team of up to four online players works together to complete missions in the mall.