Years after the Reploid Wars, all seems peaceful in the world. But peace was not meant to last forever. When the "Eurasia" space colony is attacked by an unknown virus, the call goes out! X and Zero are called back into action to help destroy the colony, which is now on a collision course with Earth, and is expected to collide into the planet in only 16 hours! At the same time, Sigma, the archenemy of the Maverick Hunters, shows up again...

Mega Man X5 retains the gameplay style of the previous games, adding new features such as advanced Maverick AI, bigger and more challenging stages, and new gameplay elements: ducking and swinging on vines and ropes.