"Yuzuki-san Chi no Yon-Kyōdai" centers on the lives of the four Yuzuki brothers—Hayato, Mikoto, Minato, and Gakuto—who navigate the challenges of growing up after the loss of their parents. The eldest, Hayato, assumes the role of caretaker, balancing his responsibilities as a high school student with the demands of raising his younger siblings. Mikoto, the second eldest, is pragmatic and often clashes with Hayato over their differing approaches to family matters. Minato, the third brother, is sensitive and artistic, while Gakuto, the youngest, is energetic and curious, often providing comic relief.

The narrative explores the dynamics of sibling relationships, highlighting both the struggles and joys of their shared life. Each brother grapples with personal growth, school, and societal expectations, while also dealing with the emotional weight of their parents' absence. The story delves into themes of resilience, responsibility, and the importance of family bonds, portraying how the brothers support one another through everyday challenges. Moments of humor and warmth are interwoven with poignant reflections on loss and maturity, creating a balanced portrayal of their lives. The series captures the essence of familial love and the complexities of growing up in a household shaped by adversity.