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Tokyo Red Hood is about an eleven year old girl who usually just goes by the name of Akazukin (Little Red Riding Hood). She has a sick obsession with a being known only as Mr. Wolf and wants nothing more than to be eaten by him to end her "immortal" life. Akazukin has lost all of her memories and doesn't even know who she really is. Her reason to want to be eaten by Mr. Wolf is not even known to her, instead it's a desire that is locked deep within her consciousness.
The beings of the world are mainly made up of two forces. The people who aid Akazukin in her search for Mr. Wolf, and the people who try to keep Akazukin away from Mr. Wolf. The people of the church and disciples of God try to keep Akazukin from completing her mission to meet Mr. Wolf. Their reason for doing this is because if Akazukin is eaten by the Wolf, it would bring along an end to the world and humankind as it exists in the present day. The people whose origins are from the underworld aid Akazukin to find Mr. Wolf so the fate of the world being destroyed can be fulfilled. They mainly do this discreetly and behind the shadows.
Akazukin works as an organ harvester for an Italian butcher named Marco. From there she hunts new bodies for him and all the while tries to find Mr. Wolf. Along the way she meets villains who stand in her way from fulfilling her wish to be eaten by Mr. Wolf.