This study investigated gender- and age-based differences in the quality of life (QoL) of residential school adolescents using the WHOQOL-BREF framework. A total of 216 students from residential schools in West Bengal, India, participated in the study (Male 14–15 years: n = 68; Male 16–17 years: n = 46; Female 14–15 years: n = 51; Female 16–17 years: n = 51). Participants were assessed across four Quality of Life (QoL) domains: physical health, psychological health, social health, and environment. A multivariate analysis of variance (MANOVA) was conducted to examine the combined effects of gender and age, followed by univariate analyses to identify domain-specific differences. The results revealed a significant gender difference only in the physical health domain, with males reporting higher physical health than females. No gender differences were found in psychological, social, or environmental domains. However, significant age differences emerged in these three domains, with younger adolescents reporting better overall QoL than older students. The findings highlight developmental and contextual influences on adolescents’ lived experiences and underscore the need for residential schools to implement age-sensitive psychosocial support mechanisms to promote holistic well-being. These findings have implications for educational planning and student support systems in residential school settings.