"Nighthead Genesis" is a 24-episode anime series that adapts the supernatural drama manga by Baku Yumemakura and You Higuri. The narrative centers on the Kirihara brothers, Naoto and Naoya, who possess psychic abilities. After their parents' mysterious death, the brothers are confined to a research facility by the government, which seeks to study and control their powers. Naoto, the elder brother, has telekinetic abilities, while Naoya, the younger, is a powerful medium capable of communicating with spirits and foreseeing the future.

The brothers escape the facility and embark on a journey to uncover the truth behind their parents' death and the origins of their powers. Their quest leads them to confront various supernatural entities, including malevolent spirits, demons, and other psychics. Along the way, they encounter allies and adversaries, such as Shouko Kirihara, a government agent with her own agenda, and Kuroki, a mysterious figure with ties to the brothers' past.

The series explores themes of isolation, the struggle for freedom, and the ethical implications of wielding extraordinary powers. The brothers' bond is a central focus, as they navigate a world that fears and exploits their abilities. The narrative delves into the consequences of their powers, both for themselves and those around them, as they grapple with the moral dilemmas of using their abilities to protect or harm others.

As the story progresses, the brothers uncover a larger conspiracy involving a secret organization that seeks to manipulate psychic phenomena for its own ends. This organization, known as the "Nighthead," plays a pivotal role in the brothers' journey, forcing them to confront their own identities and the true nature of their powers. The series builds toward a climactic confrontation that tests the limits of their abilities and their resolve to forge their own path in a world that seeks to control them.