"Neuro - Supernatural Detective" centers on Yako Katsuragi, a high school student who becomes entangled in a world of supernatural mysteries after encountering Neuro Nōgami, a demon from the underworld. Neuro, a being who feeds on "puzzles," has come to the human world to solve complex cases and satiate his hunger. He forms a contract with Yako, using her as his assistant to investigate crimes while he remains invisible to others. In exchange, Neuro promises to help Yako uncover the truth behind her father's mysterious death, a case that has haunted her for years.

The narrative unfolds through a series of episodic cases, each presenting intricate puzzles and crimes that require Neuro's cunning intellect and Yako's growing deductive skills. Neuro's methods often involve manipulating human psychology and exploiting the weaknesses of criminals, showcasing his ruthless and calculating nature. Despite his demonic origins, Neuro's character is layered, blending dark humor, arrogance, and occasional glimpses of empathy. Yako, on the other hand, evolves from a passive observer to an active participant, gradually developing her own investigative abilities and moral compass.

The series explores themes of justice, morality, and the blurred lines between good and evil. Neuro's presence challenges conventional notions of right and wrong, as his actions often prioritize solving puzzles over ethical considerations. Yako serves as a counterbalance, questioning Neuro's methods and striving to uphold her own sense of justice. Their dynamic is central to the story, oscillating between partnership and conflict as they navigate the complexities of each case.

Supporting characters, such as Detective Godai and Akane, add depth to the narrative, providing additional perspectives on the cases and the moral dilemmas they present. The series also delves into the backstories of key characters, revealing connections to the overarching mystery of Yako's father's death. As the story progresses, the episodic format gives way to a more serialized plot, with the stakes escalating as Neuro and Yako confront increasingly dangerous adversaries and uncover deeper conspiracies.

"Neuro - Supernatural Detective" combines elements of mystery, supernatural fiction, and psychological drama, creating a compelling narrative that balances episodic storytelling with an overarching plot. The interplay between Neuro and Yako drives the series, offering a unique exploration of human and demonic motivations within the framework of detective fiction.