"Mamekichi Mameko NEET no Nichijō" is a slice-of-life manga that centers on the daily life of Mameko, a young woman who identifies as a NEET (Not in Education, Employment, or Training). The narrative unfolds in a lighthearted and comedic manner, capturing the mundane yet quirky aspects of Mameko's existence as she navigates her unconventional lifestyle. Mameko lives with her older brother, Mamekichi, who serves as her primary caretaker and source of financial support. Despite her lack of traditional employment, Mameko finds ways to fill her days with various hobbies, interests, and interactions with her small circle of friends.

The story explores Mameko's relationships with those around her, including her brother, who often finds himself exasperated by her antics but remains supportive. Mameko's daily routines are punctuated by her unique perspective on life, which often leads to humorous misunderstandings and situations. Her interactions with her friends, who also have their own quirks and struggles, add depth to the narrative, showcasing a range of personalities and dynamics. The manga does not follow a strict overarching plot but instead presents a series of episodic vignettes that highlight the humor and occasional poignancy of Mameko's life.

Themes of self-acceptance, familial bonds, and the challenges of societal expectations are subtly woven into the story. Mameko's NEET status is not portrayed as a failure but rather as a deliberate choice, and the manga examines the complexities of her decision without passing judgment. The tone remains consistently light and comedic, with moments of introspection that add emotional resonance. The characters are well-defined, each contributing to the series' charm through their distinct personalities and interactions. Overall, "Mamekichi Mameko NEET no Nichijō" offers a humorous and relatable look at an unconventional lifestyle, blending comedy with heartfelt moments in a way that resonates with readers.