"Komori-san wa Kotowarenai!" centers on Shuri Komori, a high school girl with an overwhelming inability to say no to requests from others. Her extreme helpfulness often leads to comedic and chaotic situations as she goes to great lengths to fulfill even the most trivial or absurd demands from her classmates, teachers, and even strangers. Despite her good intentions, her inability to set boundaries frequently results in over-the-top scenarios that test her patience and physical limits.

The series explores Shuri's daily life as she navigates the challenges of being a perpetual people-pleaser. Her classmates, particularly her close friend Miki Takekasa, often try to intervene or help her manage her tendency to overcommit, but Shuri's determination to assist others usually overrides their efforts. The narrative is episodic, with each episode presenting new requests and situations that highlight Shuri's unwavering dedication to helping others, no matter how inconvenient or bizarre the task may be.

Shuri's character is defined by her boundless energy, kindness, and occasional naivety, which make her both endearing and frustrating to those around her. The supporting cast, including Miki and other classmates, provide a contrast to Shuri's personality, often serving as the voice of reason or comedic foils. The series balances humor with moments of genuine warmth, showcasing the impact of Shuri's actions on her relationships and the people she helps.

The plot does not follow a continuous storyline but instead focuses on self-contained episodes that emphasize Shuri's interactions and the consequences of her inability to refuse requests. This structure allows for a variety of comedic and situational humor, often escalating to absurd levels as Shuri's efforts spiral out of control. Despite the comedic tone, the series occasionally touches on themes of selflessness, the importance of setting boundaries, and the value of genuine kindness in a lighthearted and accessible manner.