Harley's Humongous Adventure follows the story of Harley, a young scientist with an extremely high IQ. While experimenting with a shrinking machine, an accident occurs and Harley finds himself miniaturized to the size of a bug. With his regular size nowhere in sight, Harley must navigate through treacherous terrain to gather the missing parts of his machine and reassemble it. This journey takes him through various obstacles, including commanding a tank, parachuting, using a jet pack, and battling a gigantic rat. From the perspective of an insect-sized hero, everything appears enormous.
The gameplay revolves around guiding Harley through levels, each presenting unique challenges and puzzles to solve. As Harley navigates his environment, players must utilize his small size to overcome obstacles, such as avoiding giant feet or using tiny objects to unlock doors. The game requires strategic thinking and precise control, making it an exciting and demanding experience.