"Mission-E" is a 12-episode anime series that blends science fiction, comedy, and action. The story centers on Class 2-C at Yoyogi Academy, where a seemingly ordinary high school student, Kotaro Kannazuki, becomes entangled in a series of extraordinary events. Kotaro possesses a unique ability to nullify electromagnetic waves, making him immune to electronic devices and technology. This ability draws the attention of Misaki Tachibana, a transfer student who is secretly an agent of the mysterious organization "Mission-E." The group specializes in investigating and combating individuals with supernatural or technological powers that threaten society.

Misaki is tasked with monitoring Kotaro, as his ability could potentially disrupt the balance of power. However, their relationship evolves from suspicion to collaboration as they face various threats together. These threats often come in the form of "E-Code" users—individuals who have developed dangerous abilities due to exposure to electromagnetic phenomena. Each episode typically features a new E-Code user, with Kotaro and Misaki working to neutralize the threat while uncovering the larger conspiracy behind these occurrences.

The narrative explores themes of technology, human evolution, and the ethical implications of power. Kotaro's ability serves as both a blessing and a curse, as it isolates him from the modern, technology-driven world while also making him a key figure in Mission-E's operations. Misaki, on the other hand, struggles with her dual identity as a student and an agent, often questioning the morality of her missions. Supporting characters, such as Kotaro's classmates and other Mission-E agents, add depth to the story, providing both comedic relief and additional perspectives on the central conflicts.

The series balances episodic storytelling with an overarching plot, gradually revealing the origins of E-Code users and the true motives of Mission-E. The dynamic between Kotaro and Misaki drives much of the narrative, as their contrasting personalities and shared experiences create a compelling partnership. By the end of the series, the stakes escalate, leading to a climactic confrontation that tests their resolve and challenges their understanding of power and responsibility.