South Asia comprises a socio-culturally and economically homogenous group of countries with complex geo-political relationships. These countries are the home to a sizeable population. The current chapter introduces the uniqueness of this region and the unique attributes regarding their vulnerabilities and healthcare outcomes. The factors that govern these vulnerabilities are not merely the direct effect of the causative factors but also due to the complex interplay with other related stakeholders. A similar pattern was also observed while reviewing this population’s potential social determinants of mental health. We could identify certain factors that are known to play a role universally across all population groups (like age, gender, educational status, and socio-economic status). Additionally, we could identify further determinants that are pertinent to this region owing to its geo-political situation (e.g., migration, minority affiliation, socioeconomic deprivation, etc.). The current state of research points to a need for intervention measures to target the determinants to improve the mental health conditions of the residents. Both governmental and non-government sectors have initiated a number of measures in this regard. However, there is still a need for better appreciation of the situation and the introduction of newer strategies with more intersectoral collaboration backed by political will.