Endometriosis is a chronic gynecological condition with profound consequences. Despite increasing research, studies on health-related quality of life (HRQoL) in endometriosis remain fragmented, often neglecting the interplay between medical and psychosocial aspects. This narrative review aims to provide an integrated perspective on the medical and psychosocial factors influencing HRQoL in individuals with endometriosis. A comprehensive literature search identified peer-reviewed studies examining both qualitative and quantitative research. Medical aspects such as chronic pain, dysmenorrhea, infertility, dyspareunia, fatigue, and treatment side effects were strongly associated with reduced HRQoL. Psychosocial aspects included depression, anxiety, self-esteem, body-image, coping strategies, illness perceptions, and social and work-related challenges. Treatment-related aspects, including diagnostic delay and patient-centered care, emerged as important factors associated with HRQoL. The findings highlight the necessity of a holistic approach to improve patients’ HRQoL. However, research on the implementation and effectiveness of such approaches remains scarce. Future research should prioritize adolescents, longitudinal designs, and integrative analytic frameworks to better capture both short and long-term effects of the complex interactions between medical and psychosocial factors relevant to HRQoL in those affected.