"Muhyo & Roji's Bureau of Supernatural Investigation" centers around the partnership between Muhyo, a prodigious legal executor of magic law, and his assistant, Roji, as they tackle supernatural cases involving spirits, demons, and otherworldly entities. The duo operates a small bureau specializing in resolving disputes and conflicts caused by these supernatural forces, often involving clients who are haunted or cursed. Muhyo, despite his youthful appearance, is a highly skilled and authoritative figure in the field of magic law, wielding powerful techniques to banish or punish malevolent spirits. Roji, on the other hand, is more grounded and empathetic, often serving as the emotional anchor for their team.

The narrative unfolds through episodic cases, each presenting unique supernatural challenges. These cases range from exorcising vengeful spirits to negotiating with powerful demons, showcasing the duo's resourcefulness and teamwork. As the series progresses, deeper layers of the magic law system are revealed, including the existence of the Magical Law School, where Muhyo and Roji trained, and the Enforcement Bureau, a larger organization overseeing supernatural affairs. The dynamic between Muhyo and Roji is central to the story, with Muhyo's stern and often abrasive demeanor contrasting with Roji's kindness and determination.

Key characters include Nana, a former classmate of Muhyo and Roji who becomes a recurring ally, and Biko, a skilled executor with a mysterious past. The series also introduces antagonists such as Enchu, a rogue executor with a personal vendetta against Muhyo, and various powerful demons who challenge the protagonists' abilities. The plot gradually builds toward larger conflicts, including Muhyo's past and the darker aspects of the magic law system, culminating in high-stakes battles and revelations about the true nature of their world.

The anime balances episodic storytelling with an overarching narrative, blending action, humor, and moments of emotional depth. It explores themes of justice, loyalty, and the consequences of wielding power, all while maintaining a focus on the partnership between Muhyo and Roji as they navigate the complexities of their supernatural profession.