"Jinsei" centers around the daily lives and interactions of students in the Modern Literature Club at Shinyo High School. The protagonist, Ayaka Nikaido, is a highly intelligent and disciplined third-year student who serves as the club's president. Her pragmatic and no-nonsense demeanor often contrasts with the more carefree attitudes of her fellow club members. The series explores various scenarios and dilemmas faced by the students, often framed as life advice or philosophical questions, which are presented through letters submitted to the club's advice column.

The narrative structure is episodic, with each episode addressing a new letter or problem. These issues range from personal struggles, such as relationships and self-confidence, to more lighthearted topics like school festivals and club activities. Ayaka, along with her clubmates—Rino Endo, a cheerful and optimistic second-year student, and Fumi Kujo, a reserved and bookish first-year—collaborate to provide thoughtful and often humorous solutions. The interactions between the characters highlight their distinct personalities and the dynamics of their friendships.

Throughout the series, the Modern Literature Club encounters a variety of other students and faculty members, each contributing to the diverse array of situations explored. The tone of the series balances humor with moments of introspection, offering a blend of comedic and thoughtful storytelling. The episodic nature allows for a wide range of themes to be addressed, making the series accessible and relatable to a broad audience. The characters' growth and the evolving dynamics within the club serve as a consistent thread, tying the individual episodes together into a cohesive narrative.