Fuse is a third-person shooter where the player takes the role of a member of the elite Overstrike 9 squad. In the future, a group of four misfit agents join together and form Overstrike 9, a team that aims to stop the evil Raven Corporation and their leader, named Fable, from gaining an alien power supply called Fuse. The game revolves around the four agents of the Overstrike 9 team: Dalton Brooks, a mercenary, Naya Deveraux, a former Raven Corporation employee, Isabelle "Izzy" Sinclair, a young scientist, and Jacob Kimble, a decorated detective. Each agent brings a set of abilities that is unique to each character. For example, Dalton, a more defensive oriented character, possesses an expandable shield that has the ability to catch bullets and other enemy fire and then throw them back. Jacob, a more damage driven character, has a crossbow that deals a large amount of damage to enemies.

Fuse is a game of teamwork. Through the LEAP system, players switch back and forth from character to character during battle, allowing you to utilize each agent's specific skill set. The game allows for two-player split-screen co-op with up to four players in co-op online. As you progress through the game, players gain experience to unlock abilities and upgrade weapons. In addition, each agent is equipped with a unique skill tree that allows for further customization of each character.