Skeletal muscle, as one of the largest organ system in the human body, exerts a determining influence on adolescents’ mastery of motor skills and their lifelong health. Puberty represents a critical window for muscle development, during which the quality of myogenesis not only shapes athletic potential but also profoundly influences long-term health outcomes in adulthood. Under pathological conditions, such as obesity, an aberrant metabolic environment can compromise muscle function in youth, impede the progression of motor abilities, and increase susceptibility to metabolic disorders. It is well established that scientifically prescribed exercise interventions effectively unlock adolescents’ muscle-building potential, thereby laying a solid foundation for enduring physical performance and overall well-being. This chapter offers a systematic overview of the key biological principles that regulate skeletal muscle development during puberty and provides an in-depth analysis of the mechanisms and signaling pathways by which structured exercise drives muscle growth and functional adaptation. In addition, it examines the challenges posed by muscle structural and functional impairments under pathological states and evaluates how targeted exercise regimens can restore and enhance muscle health. By mastering the conceptual framework presented here, coaches and parents will be better equipped to identify early warning signs of impaired muscle development, support individualized training plans that optimize motor skill acquisition while minimizing injury risk, and implement proactive interventions to prevent metabolic dysregulation and age-related muscle decline.