"Comic Girls" centers on Kaoruko Moeta, a high school student and aspiring manga artist who struggles with self-doubt about her work. After receiving feedback that her manga lacks impact, Kaoruko moves into a dormitory called Himetama House, which is specifically for female manga creators. There, she meets three other residents: Koyume Koizuka, a shoujo manga artist with a flair for romantic storytelling; Ruki Irokawa, a reserved and serious creator of action-packed manga; and Tsubasa Katsuki, a mature and experienced artist who writes fantasy manga. Each character represents a different genre and approach to manga creation, providing a diverse perspective on the creative process.

The series explores the daily lives and challenges faced by these young artists as they navigate the pressures of deadlines, creative blocks, and personal insecurities. Kaoruko, in particular, grapples with her lack of confidence and often seeks encouragement from her peers. Koyume, despite her bubbly personality, struggles with balancing her personal life and her work, while Ruki faces the challenge of stepping out of her comfort zone to connect with others. Tsubasa, the most experienced of the group, often acts as a mentor but also deals with her own struggles, including the pressure to maintain her success.

Throughout the series, the characters support one another, sharing advice, collaborating on projects, and celebrating their successes. The narrative highlights the camaraderie and mutual respect among the residents of Himetama House, emphasizing the importance of community in overcoming creative and personal obstacles. The story also delves into the technical aspects of manga creation, offering insights into the industry and the dedication required to succeed as a professional artist.

"Comic Girls" balances lighthearted humor with moments of introspection, portraying the joys and struggles of pursuing a creative career. The interactions between the characters are central to the narrative, showcasing their growth as individuals and as artists. The series provides a realistic yet optimistic portrayal of the challenges faced by young creators, making it a relatable and engaging story for audiences interested in the world of manga and artistic expression.