While research in specific academic disciplines has individually advanced knowledge and practice for promoting multiple aspects of health and well-being in children and adolescents, still missing is an understanding of the interconnectedness of many critical aspects of development and how to intentionally weave these factors to advance a more holistic approach. The need for a more holistic and inclusive approach to child and adolescent development is increasingly evident to promote long-term health and well-being as the overall percentage of children, adolescents, and adults who suffer from mental health disorders is increasing. To address this issue, our authorship team consists of researchers in the areas of developmental psychology, neuroscience, motor development, exercise science, and mental health. The collective ideas outlined in this paper are aligned to address the need to remove disciplinary-specific boundaries and elucidate synergistic linkages across multiple research domains that support holistic development and lifespan health and wellness. We propose a conceptual framework that comprehensively addresses the integration of physical, cognitive, psychological, social, and emotional domains of child and adolescent development. In addition, we also provide a holistic preventative approach that is aligned with a contemporary intervention structure (i.e., Multi-tiered Systems of Support) to promote, from a developmental perspective, positive trajectories of health and well-being across childhood and adolescence.