Mexican male to female transgender asylum seekers in the United States suffer from serious health issues that can be attributed to stressors related to their transgender, ethnic minority, and socioeconomic status. This study explored these stressors, the resulting health issues, and the needs of this particularly vulnerable population. Asylum seekers’ (n = 45) sworn declarations and psychological evaluations were examined by a multidisciplinary research team using a systematic document review process. The review identified stressors that occurred both in Mexico and the United States: verbal, physical, and sexual assaults; unstable environments; fear for safety/security; hiding undocumented status; and economic insecurity. The health issues that resulted in part from these stressors include posttraumatic stress disorder, depression, anxiety, sleep issues, isolation, avoidance, drug/alcohol use, and suicidal tendencies. Despite suffering from multiple health issues, asylum seekers rarely sought health or social services. Health promotion practitioners can play an important role in serving this silent minority by (1) expanding community-based research focused on the intersection of transgender, ethnic minority, and socioeconomic status; (2) using trusted community members to connect this population to necessary resources; (3) providing communication training/resource development for health care providers; and (4) creating a network of service organizations that understand the needs of transgender asylum seekers.