Dead Rising 4 is the fourth main game in the open world survival horror series and the eighth installment overall. It is set during September 2021, one year after the events of Dead Rising 3 and sixteen years after the original Dead Rising. The protagonist is Frank West, formerly a freelance photographer and now a professor at a community college, returning as the lead from some of the earlier titles. The prologue is a nightmare in the Willamette Park View mall in Colorado from his earlier days during the zombie outbreak. When he wakes up he receives a message from his his rebellious protege Vick Chu who drives him to Willamette. West thinks they go there to play minigolf, but Chu actually wants to look into a secret military base with him where human trials are supposed to take place. After sneaking into the base which serves as a tutorial, soon the scenes from his nightmare become reality again, set in winter during the Christmas period.

As before the game 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 with over-the-top and slapstick violence. The game again uses an extensive crafting system where players can create and customize their own weapons along with building many types of vehicles. Weapons include for instance the Gandelf, combining a spear and a garden elf to shoot exploding elves and a slam attack. West gets to explore Willamette which has changed a lot since his last visit. The mall from the original Dead Rising has been turned into the central Willamette Memorial Megaplex. At the same time he also gets to explore the surrounding neighbourhoods. As usual there are a lot of items to discover and collect such as weapon blueprints and hidden graffiti art to photograph. There are also many side quests, hidden bosses known as Maniacs and additional investigations to pursue along with events to rescue survivors or destroy military equipment. There is more time to explore as the game no longer employs a countdown timer to urge the character forward. Shelters serve as safe havens to acquire new vehicles, weapons and maps that reveal collectibles in the environment. Experience provides skill points used to upgrade abilities.

Photography plays a role now, as West can use a camera during investigations with different filters for night vision, to detect clues or to take selfies, similar to the Batman: Arkham games. Another new element is the introduction of an Exo Suit. It briefly makes West extremely powerful, allowing him to tear through the environment and the groups of enemies. Some opponents can use it too. Enemies no longer get powerful at night during the day-night cycle, but there are new enemy types such as the soldiers from the Obscuris organization and the suicidal "freshies", humans that have only just turned into zombies. 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 no longer for the main campaign. Instead there are now four separate episodes where a team of up to four online players works together to complete missions in the mall.