The aim of this systematic review was to identify the issues related to the vulnerability and psychosocial risk factors of people who identify as transgender. A search of relevant electronic databases from 2007 to 2017 was conducted. Included studies involved transgender people, vulnerability, and risk factors. Following the application of rigorous inclusion and exclusion criteria, a total of 21 papers were considered suitable for the review. The identified themes included sexual risks, substance use, psychological vulnerability risk factors, and protective factors and behaviors. Nurses are in a strong position to address pertinent concerns and to provide the necessary psychosocial supports to this population.