Players navigate the open world of Sunset City in 2027. The dystopian world has been overrun by mutants called the OverCharge Drinkers or OD for short. The player character, whose gender, skin tone, body type, hair and face can be customized, is a former FizzCo employee, tasked with cleaning up the mess left behind from a party FizzCo has thrown in celebration of the launch of their new energy drink, Overcharge Delirium XT. Players fight the OD - humans whose endocrine systems have gone into overdrive from consuming the energy drink.

In 2027, FizzCo has released their new hit energy drink, OverCharge Delirium XT. FizzCo, in an attempt to sell OCD faster, skipped health regulation protocols. Unknown to FizzCo, the drink causes everyone who consumes it to turn into hungry, violent and grotesque mutants. FizzCo, in order to cover up their mistake, and to keep stock prices up, claims that a virus has broken out in Sunset City, and quarantines the whole city, preventing any entrance or exit along with no way of connecting to the outside world. The player, a FizzCo employee, who works in the sanitation division, teams up with other survivors in an attempt to escape Sunset City and expose the truth behind Fizzco. The player must bounce on cars, run on walls and grind rails navigating the city, collecting "valuable" items that are used to purchase odd weapons and upgrades. The player must befriend factions throughout the city, and convince them to fight with him/her. In the end it was discovered that the FizzCo main office is a self-destructing building robot that is going to destroy Sunset City. The player defeats the robot and has beer with the other survivors.

The game focuses on "agile combat", including wall running, zip-lines, and acrobatics. Players use grind rails to deftly navigate city streets. On-foot, players cannot run or take cover, but instead must rely on agility to survive. Players can carry up to eight weapons at once, including the standard assault rifle AK-FU, the TNTeddy RPG that fires teddy bears strapped to sticks of dynamite, and the Flaming Compensator shotgun which fires off incendiary rounds. All weapons eventually run out of ammunition, but do not need to be reloaded while being used. Players unlock more weapons by progressing through the story or purchasing them from shops. Weapons can be upgraded by applying "Amps" that increase their lethality. The Style Meter in the head-up display (HUD) increases as players perform stylish moves like killing enemies and grinding on-rails without touching the ground.

After the credits, Protocol X23 has been activated and FizzCo helicopters are seen being sent around the world to deliver OCD.