Stressors inherent to training and stemming from the learning environment are associated with high rates of burnout, depression, and mental health problems in health professions students (HPS). There is evidence that disadvantaged or stigmatized groups are particularly affected. These problems not only impact students after graduation but may also have detrimental effects on patient outcomes. Resilience, conceptualized as the process of adapting well in the face of adversity, has inspired an increasing number of interventions aimed at addressing those problems in HPS. These interventions have mostly targeted individual students and their psychological traits while ignoring social and structural factors that may enhance or undermine individual resilience. To address this gap in the literature, the authors reviewed the evidence for psychosocial determinants of resilience and proposed a model inspired by the social determinants of health literature and the “upstream–downstream” metaphor. In this theoretical paper, the authors propose that upstream determinants such adverse childhood experiences and socioeconomic and sociodemographic markers of disadvantage have a direct effect on psychological adjustment and an indirect effect mediated by resilience. Additionally, the authors propose that the institutional downstream drivers of learning environment, social support, and sense of belonging moderate the direct and indirect effects of the upstream determinants on psychological adjustment. Future research should test these hypotheses and gather evidence that may guide the development of interventions. The authors present their model as part of a comprehensive response to recent calls to action to address diversity, equity and inclusion in health professions education.