Background: Depression is a prevalent mental health concern among medical students, with signifi cant implications for Health-related Quality of Life (HrQol). Understanding the factors contributing to depression and their impact on HrQol is crucial for developing targeted interventions to support students’ well-being. Aim: This literature review aims to assess the impact of depression and other related factors on HrQol in medical students, exploring the prevalence, associated risk factors, and implications for overall well-being. Methodology: A comprehensive search was conducted on PubMed Central and Scopus databases, focusing on studies addressing depression, burnout, anxiety, and other factors infl uencing HrQol in medical students. Inclusion criteria were applied to select relevant articles, resulting in a fi nal selection of 15 articles for detailed analysis. Data extraction included study design, sample characteristics, methodology, results, and conclusions. Results: The review revealed a high prevalence of depression among medical students, particularly among female students and those facing socio-economic challenges. Factors associated with depression include gender, socioeconomic status, obesity, chronic diseases, addiction, and academic stress. Depression was found to signifi cantly impact HrQol, leading to lower mental health-related QoL scores compared to physical health scores. Other factors such as stress levels, family support, sleep quality, and academic demands also infl uenced HrQol outcomes among medical students. Conclusion: Addressing depression and its impact on HrQol is essential to promote the overall well-being of medical students. Tailored interventions targeting depression, stress management, family support, and sleep quality are crucial for improving HrQol and mitigating the adverse eff ects of mental health challenges in this population. Keywords: Academic performance; medical student; HRQOL; Health-related quality of life.