HIV disproportionately impacts transgender communities and the majority of new infections occur in the Southern United States. Yet, limited data exists on contextual realities of HIV vulnerability and healthcare needs among transgender individuals in the Deep South. Addressing this gap in the literature, we assess the health needs, including barriers and facilitators to accessing healthcare, including and beyond HIV, from the perspective of transgender men and women in Mississippi. Between June-August 2014, in-depth, semi-structured qualitative interviews (n = 14) were conducted with adult transgender persons at an LGBT healthcare setting in Jackson, Mississippi. In-depth interviews lasted between 60-90 minutes and followed semi-structured format (themes probed: HIV vulnerability, healthcare needs, and availability of gender-affirming medical care). Audio files were transcribed verbatim and analyzed using Dedoose (v.6.1.18). Among participants (mean age = 23.3 years, standard deviation = 4.98), 43% identified as a transgender man or on a transmasculine spectrum, 43% as Black, and 21% self-reported living with HIV. HIV-related services were frequently described as the primary gateway to accessing healthcare needs. Nonetheless, participants' primary health concerns were: gender affirmation processes (hormones, silicone, binding/packing); mental health; and drug/alcohol use. Stigma and discrimination were commonly reported in healthcare settings and health-related information was primarily attained through social networks and online resources. Results highlight gender identity alongside race and pervasive marginalization as key social determinants of transgender health in Mississippi. As Mississippi is one of several states actively debating transgender access to public accommodations, findings underscore the need to treat transgender health as a holistic and multidimensional construct, including, but moving beyond, HIV prevention and care.