Cynthia Rou is a pint-sized assassin from a family of killers, living a double life as a part-time student who appears completely bald. She continuously receives assassination orders from a shadowy organization and carries them out with her unusual skills. The story begins when Cynthia and two friends are shopping for hair growth solution, and a new mission arrives: she must kill a target whose bodyguard is none other than her own former master, who trained her three years earlier. This confrontation sets the stage for a series of violent and unpredictable battles.

The manga follows Cynthia and her fellow assassins Araya Kuga and Kanae Takaya as they navigate a world of bizarre martial artists and grotesque abilities. The setting shifts across various locales, from the streets of Kowloon to the United States, where one notable arc involves a girl attempting to assassinate the U.S. president by using swastika imagery in her eyes, as revenge for the Iran War. The narrative is structured around a mix of standalone missions and longer arcs, often punctuated by over-the-top fight scenes that are gory, creative, and unpredictable. A major arc sees an entire volume devoted to flashbacks in the middle of an important storyline. Characters like the mysterious Hotaru Shimizu, the imposing Cybele Rou, and the master figure Iko Tendou add depth and conflict, while the series balances black comedy with martial arts mayhem. Throughout its run, Cynthia the Mission maintains a focus on the absurdity of its premise, the camaraderie among its leads, and the constant threat of lethal orders from above.