Mark of the Ninja's creation was inspired by the lack of "stealthy" ninjas in popular series such as Ninja Gaiden, of which lead designer Nels Anderson felt that omission of such a prominent trait of ninjas in popular culture felt weird.

He drew further inspiration from the Thief series, of which its core gameplay is focused on being unseen, and tried to break down and translate the character and 3D environment's stealth elements over to a 2D sidescroller.