Marvel vs. Capcom: Clash of Super Heroes is the fifth Marvel Comics-licensed fighting game by Capcom and the third game in the Marvel vs. Capcom series. In contrast to X-Men vs. Street Fighter and Marvel Super Heroes vs. Street Fighter, the game features characters from numerous Capcom franchises such as Mega Man and Strider, rather than just Street Fighter characters. The game takes place within the Marvel comic continuity, as Professor Charles Xavier calls out for heroes to stop him before he merges with the consciousness of Magneto and becomes the being known as Onslaught, the final boss.

The storyline is loosely based on the X-Men: Onslaught arc from the Marvel Comics continuity: following an incident in which mutant telepath Charles Xavier was forced to enter into the mind of Magneto, part of Magneto's anger slipped into Xavier's psyche, and after merging with Xavier's darkest emotions it spawned a powerful psychic entity known as Onslaught. The game expands on the story by having Xavier's conscience calling forth heroes from the Capcom universe in order to help stop him.