Medaka Kuroiwa is a high school student who possesses an extraordinary ability to remain completely unaffected by the charms and advances of others, particularly those of the opposite sex. This unique trait makes him impervious to the flirtatious behavior of his classmates, including the beautiful and popular Aika Tsuchiya, who is accustomed to having her way with boys. Aika, intrigued and frustrated by Medaka's indifference, becomes determined to break through his emotional barrier and win his affection. Her efforts to seduce him form the central conflict of the series, as she employs various strategies, from subtle manipulation to outright boldness, all of which fail to elicit the desired reaction from Medaka.

The narrative explores the dynamics of their interactions, with Aika's persistence and Medaka's unwavering stoicism creating a comedic and often absurd tension. Medaka's imperviousness is not merely a personality quirk but a deeply ingrained trait that stems from his logical and pragmatic worldview. He views romantic overtures as illogical and unnecessary, which further complicates Aika's attempts to connect with him. Despite her initial motivations being rooted in vanity and curiosity, Aika's character gradually develops as she begins to question her own intentions and feelings.

Supporting characters, such as Medaka's childhood friend and confidant, provide additional layers to the story, offering insights into Medaka's past and his reasons for maintaining emotional distance. The series balances humor with moments of introspection, as Aika's relentless pursuit forces both characters to confront their own vulnerabilities and misconceptions about relationships. The interplay between Medaka's rationality and Aika's emotional drive creates a compelling dynamic, with the story often highlighting the absurdity of their situation while subtly exploring themes of human connection and self-awareness. The series maintains a lighthearted tone, using exaggerated scenarios and comedic timing to underscore the central premise while allowing room for character growth and development.