"The 3-Mei-sama: Anime wa Anime de Arissho!" centers around three high school girls—Mei, Mei, and Meiko—who share a unique bond and a shared passion for anime. Each girl embodies a distinct personality and perspective on life, which often leads to humorous and heartfelt interactions. Mei is the energetic and impulsive leader, Meiko is the calm and analytical thinker, and Meii is the shy yet deeply creative dreamer. Together, they navigate the challenges of adolescence while immersing themselves in the world of anime, often drawing parallels between their own lives and the stories they love.

The narrative unfolds as the trio forms an anime club at their school, aiming to share their enthusiasm with others. Their club activities range from watching and discussing classic and contemporary anime to creating their own fan works, such as doujinshi and cosplay. The series explores their struggles to balance their passion with academic responsibilities, social expectations, and personal growth. Along the way, they encounter a diverse cast of classmates and teachers, each with their own quirks and connections to anime culture.

Key plot arcs include the girls organizing a school festival event centered around anime, competing in a local cosplay contest, and collaborating on an original anime project. These events serve as catalysts for character development, highlighting their strengths, insecurities, and evolving friendships. The series also delves into themes of creativity, self-expression, and the impact of media on personal identity, all while maintaining a lighthearted and comedic tone.

The dynamic between the three protagonists drives the story, with their contrasting personalities creating both conflict and camaraderie. Mei’s boldness often clashes with Meiko’s cautious nature, while Meii’s imaginative ideas provide a bridge between the two. Their shared love for anime serves as a unifying force, allowing them to overcome obstacles and grow closer as friends. The series balances episodic humor with overarching character arcs, offering a blend of relatable high school experiences and meta-commentary on anime fandom.