Transgender women (TGW) are disproportionately affected by sexually transmitted infections (STIs). Experienced trauma threatens TGW's commitment to sexual healthcare. Trauma-informed approaches to sexual healthcare can improve engagement. This study aimed to characterize the trauma experienced by TGW in the Southeastern US, especially related to sexual health. TGW completed in-depth individual interviews guided by the Modified Social Ecological Model (MSEM) and Minority Stress framework. Interviews explored the nature of trauma, sexual health, and their intersection in TGW's lives, and a thematic analysis was performed. Between August 2022 and January 2023, 13 TGW enrolled (69% Black, 31% White). Mental illness was common (77%). Five participants (38%) were HIV+, and seven (54%) reported lifetime STI history. Themes reflected societal (barriers to healthcare, anti-transgender legislation), community (misgendering/deadnaming), network (limited support), and individual (dysphoria, sex work, fear for physical safety, stigma, mental health conditions, race) stressors. The physical/sexual violence and resilience themes pervaded all stressor levels. Medical mistrust was exacerbated by past traumatic experiences within sexual healthcare settings. Resilience and transgender representation in healthcare settings were protective. Various experienced traumas and their cumulative effects were pervasive in the daily lives of TGW. Development of targeted interventions to improve sexual health engagement of TGW must optimize personal strengths and provide holistic support.