Background Stroke is the second leading cause of mortality globally, with 70% of cases occurring in low- and middle-income countries. Various risk factors for stroke have been identified as predictors of Health-Related Quality of Life (HRQoL). Objective This study aims to assess the impact of associated factors of stroke on the quality of life (QoL) of stroke patients at this tertiary hospital in Nepal. Method A descriptive cross-sectional study was conducted among 92 stroke patients at Annapurna Neurological Institute and Allied Sciences from June to December, 2022. Data were collected through a pre-designed and pre-tested SS-QoL questionnaire followed by a face-to-face interview. SPSS version 22 was employed for analysis, and Mann-Whitney U tests and Kruskal-Wallis H tests was applied to determine the association of variables at a 5% level of significance. Result About two-thirds of the participants were male, indicating a male predominance. Patients aged 45-55 exhibited higher quality of life in family roles and vision, possibly due to the adversity of stroke in older patients. Ischemic stroke was three times more prevalent than hemorrhagic stroke, and those individuals reported higher quality of life, particularly in work and productivity. However, other domains remained statistically insignificant. Among the studied comorbidities, hypertensive patients had the highest overall quality of life. Conclusion Conducting a comprehensive evaluation of the overall quality of life in individuals who have experienced a stroke can contribute to improved health outcomes, particularly in terms of their functioning and well-being in psychosocial aspects.