HIV-related comorbidities in underrepresented minority populations are reframed to include the co-occurring problems of systemic and structural barriers, within the mentoring context as a buffer and as action-oriented. This framework is discussed to improve racial and ethnic minority diversity in the research workforce from the perspectives of HIV comorbidities and mentoring. An integrated and coordinated approach to HIV-related comorbidities and inequities may be helpful when combined with research on the social-structural contributions as drivers to diversify the research workforce. We emphasize how these key research issues (a) provide a platform for training and retraining a highly motivated, diverse workforce and (b) facilitate the empowerment of these trained individuals to conduct rigorous scientific research on social-structural factors to mitigate the effects of these comorbidities. We conclude that a diverse research workforce is necessary but insufficient for improving training-related outcomes or reducing comorbidity effects. Additional considerations are warranted that include systemic approaches and changes at the structural and institutional levels.