<p>Fifty years after George L. Engel proposed the biopsychosocial model to replace biomedical reductionism, its influence across medical disciplines, including psychiatry, endures but its scientific potential remains unrealized. Conceived as a foundation for research, education and clinical practice, Engel’s model anticipated the current search for integrative explanations linking biological, psychological and social processes. Yet in practice, it has often become a checklist rather than a causal framework. Contemporary tools, including computational modeling, network analysis, digital phenotyping and causal inference methods, enable increasingly sophisticated modeling and partial testing of these interactions across different levels of organization. This Perspective calls for a causal biopsychosocial framework to guide the next fifty years of research, teaching, and patient care that integrates measurable and predictive sciences of interacting systems to unite medicine and psychiatry.</p>