Abuse resembles a side-scrolling platform game. The game is marked for its unusual control scheme: The keyboard is used to move Nick, while the mouse is used for aiming the weapons. The basic gameplay consists of fighting various enemies (mostly the various forms of mutants, who prefer to attack in huge swarms) and solving some simple puzzles, most involving switches.

The protagonist of the game, Nick Vrenna, has been unjustly incarcerated in a prison where the staff are performing unethical medical experiments upon the inmates. A prison riot occurs and an experiment goes horribly wrong. The people inside the prison - except for Nick, who seems to be immune - get infected with a substance called Abuse that transforms them into monsters. Nick takes a laser gun and goes on to single-handily destroy all mutants, stop the substance from spreading further, and escape from the prison complex.