In Pakistan, the incidence of HIV/AIDS is rising, particularly among transgender individuals, who face significant marginalization in various aspects of life, leading to compromised health-related quality of life (HRQoL). This study aimed to assess the HRQoL of transgender individuals living with HIV/AIDS and explore its correlation with social disparities. Using the validated WHO EQ-5D-5L scale, HRQoL was evaluated among 106 transgender patients with HIV/AIDS from Mayo Hospital and Fountain House Hospital, Lahore, Pakistan, following ethical considerations with PACP. Data analysis employed the Mann-Whitney and Kruskal Wallis tests. The research revealed that HIV/AIDS moderately impacts the HRQoL of transgender individuals due to physical, psychological, and social factors. Comorbidities further exacerbated the HRQoL among this population. In conclusion, managing multiple health issues, including comorbidities, can substantially diminish the quality of life for transgender individuals with HIV/AIDS. Hence, comprehensive healthcare services should address both HIV/AIDS and associated comorbidities to ensure holistic care.