Perinatal substance use in the South Asian community is an enigmatic bio-psycho-social phenomenon for researchers and clinicians. It is a culmination of the unique challenges associated with pregnancy, matrescence, and challenges faced by women drug users in male-dominated societies. Regional data scarcity obscures the actual prevalence of illicit drug misuse and associated risk factors in this population in this region. Culturally adapted screening tools and trauma-informed care models are urgently needed to address these intersecting risks. This chapter highlights the key epidemiological characteristics, a comparison with other regions, and the specific health outcomes for both mother and child. The unique screening tools for perinatal drug use, key psychopharmacological considerations for pregnant and lactating women dealing with substance use disorder management, and the unique psychosocial treatments that work are also discussed. The chapter concludes with a list of policy considerations that will improve how this perinatal substance use is dealt with in the South Asian region.