This policy brief synthesises evidence of structural and socio-cultural determinants of transgender women's disproportionate HIV, sexually transmitted infections (STIs) and tuberculosis (TB) burden. Embedding HIV, STI and TB services for transgender women in a comprehensive gender-affirming care (GAC) model improves prevention and treatment outcomes and forms the bases of recommendations to integrate GAC through reforms in the current implementation of policies and practices. The brief is underpinned by a participatory approach and written in collaboration with trans-led organisations to harness their voices, lived experiences and practices of this marginalised group. These lived experiences reflect the resilience of transgender women as they continue to advocate for GAC and HIV, STIs and TB prevention, care and treatment for transgender women, and are useful in informing contextualised policy responses that are responsive to transgender women's healthcare needs. The organisations include established NGOs such as GenderDynamiX (GDX), the Social, Health and Empowerment Feminist Collective of Transgender Women of Africa (S.H.E), peri-rural based trans-led organisations such as the Trans Wellness Project and Uthingo Network (formerly known as the Gay and Lesbian Network) and recently established organisations: Trans Tec SA, Trans Hope Care Center and Iphimbo Lothingo. While the focus is on HIV, STIs and TB, other healthcare concerns of transgender women are also prioritised as reflected in the integrated gender-affirming approach that guides this policy brief.