"Kongōji-san wa Mendōkusai" centers on the daily life of Kongōji Haruto, a high school student who finds himself entangled in the peculiar antics of his classmate, Kongōji-san. Despite sharing the same surname, the two are not related, a fact that becomes a recurring source of confusion and humor. Kongōji-san is a highly eccentric and unpredictable individual, often causing trouble for Haruto through her bizarre behavior and unconventional actions. Her tendency to misinterpret situations and overreact creates a series of comedic misunderstandings, placing Haruto in awkward and often exasperating scenarios.

The narrative unfolds through episodic chapters, each highlighting Kongōji-san's peculiarities and the ripple effects they have on Haruto and their classmates. Her actions range from innocently strange to outright chaotic, such as her obsession with creating elaborate schemes or her habit of inserting herself into situations where she is neither needed nor wanted. Haruto, while frequently annoyed by her antics, gradually becomes accustomed to her presence, often finding himself reluctantly drawn into her world.

Supporting characters, including classmates and teachers, add depth to the story, reacting to Kongōji-san's behavior in ways that amplify the comedic tone. Some characters find her endearing, while others are baffled or frustrated by her unpredictability. The dynamic between Haruto and Kongōji-san forms the core of the series, with their interactions driving much of the humor and occasional moments of unexpected warmth.

The manga balances slapstick comedy with subtle character development, exploring how Haruto navigates the challenges of dealing with someone as unconventional as Kongōji-san. While the focus remains on humor, there are occasional glimpses into Kongōji-san's motivations and background, hinting at a more complex personality beneath her eccentric exterior. The series thrives on its ability to blend absurdity with relatable school life, creating a narrative that is both entertaining and grounded in the everyday experiences of its characters.