The game is set in Tokyo in the year 2049 and revolves around three characters whose home has been destroyed. As seen on the game's front cover, this trio seems human; however, they are actually bio-engineered weapons developed by a company named A.R.M.A. called "mutanoids". A notable feature of Crimson Tears is that the levels are generated on the fly using templates, as opposed to predefined game worlds that are the same every time.

The game is set in Tokyo in the year 2049 and revolves around three characters whose home has been destroyed. As seen on the game's front cover, this trio seems human; however, they are actually bio-engineered weapons developed by a company named A.R.M.A. called "mutanoids".