The game is set in New York Zero which has been divided into three zones based on the infection rate: red, yellow and green. That means there are also areas where Heller can freely roam among regular civilians as long as he does not display his powers. There is a main storyline with quests to pursue but also a large amount of freedom in exploration. He can eventually hack into the military grid Blacknet that details all military operations. From there he can choose his own missions in pursuit or the organization rather than being told to do quests.
Just like in the original game Heller has supernatural powers that allow him to sprint on buildings, make giant leaps, and land without taking falling damage. He has various fighting moves with his fists and claws, and he can lift objects and characters to hurl them towards enemies. He can also rip off a cannon from a tank for instance and use it as a weapon. Tanks can also be driven. Grabbing enemies now starts a short combat sequence and it can be used for intimidation, optionally followed by a throw or consuming a character. He can just as easily infect characters with the virus to make a bio-bomb out of them. Also present from the first game is the ability to shapeshift as he can take over a person's body and memories. When this is done without being seen he can shake off pursuers, temporarily assume the role of a soldier and use guns, or use it for infiltration. Heller has new dodging moves, heals and regains endurance over time, and he can access a sonar sense that highlights building or persons to make it easier to track them. The environment can also be viewed through a top-down map. Heller's abilities are further defined through various upgrades throughout the game, granting him new powers. They are divided over four categories (powers, skills, abilities, mutations), and a general evolution level based on experience. An entirely new range of powers stems from tendrils that sprout from Heller's arm and are used for various purposes.