The Amazing Spider-Man vs. The Kingpin for the Sega CD takes the idea and basic gameplay from the Genesis version, but makes some significant changes. There are new levels, new bosses, and an expanded set of combat moves. The player now has the freedom to select the next level or boss to tackle from a map screen. Graphics have also been redrawn and expanded from the Genesis release. However, the player can no longer rest and heal at Peter Parker's apartment, or take photographs of enemies for cash; both prominent features of the Genesis version.
Animated cutscenes with voices are new to this version, as well as a new CD soundtrack. The player can also find and collect digital versions of classic Spider-Man comics, making further use of the multimedia storage space. A password system has also been added to save the player's progress.
