Urban transgender women often experience several sociocultural co-factors which contribute to their risk of HIV infection. A transgender-specific HIV Prevention Case Management (PCM) intervention was implemented in a community HIV prevention setting and targeted reducing sex work and homelessness, increasing legal employment and income, and reducing psychological and emotional distress symptoms. Sixty high-risk transgender women were enrolled in the ten-session PCM intervention. Participants completed approximately nine out of the ten sessions (M = 8.7; SD = 2.6) and six-month follow-up evaluations were completed with 97% of the participants. Findings from baseline to follow-up evaluations demonstrated a decrease in homelessness (31.0% vs. 10.3%, p<0.01), less reliance on exchange sex as a primary source of income (41.4% vs. 22.4%, p < 0.05), and significant decreases in symptom complaints across multiple Brief Symptom Inventory sub-scales, including depression, hostility, phobic anxiety, and psychoticism (all significant at p<0.05). Further, socioeconomic improvements following the intervention were significantly associated with psychological and emotional gains. The study suggests that adding a culturally appropriate PCM intervention in a community setting is beneficial in addressing co-factors for HIV infection as well as psychological and emotional distress symptoms among this extremely high-risk population.