Assessing quality of life (QOL) in end-of-life patients is vital for understanding the complex impacts of terminal illnesses on individual well-being. This study aims to compare two widely used QOL assessment tools: the Karnofsky Performance Status Scale (KPSS) and the Short-Form-36 (SF-36) Health Survey among patients with late-stage diseases. KPSS, a clinician-rated scale measuring functional capacity, provides an objective perspective on a patient's clinical status. Conversely, the SF-36 offers a patient-reported overview across eight dimensions, including physical and mental health. The study enrolled 68 patients with an average Karnofsky score of about 37. Results demonstrate a significant interaction between Karnofsky scores and SF-36 dimensions, indicating that patients with higher Karnofsky scores reported better physical, social, and emotional functioning. Strong positive correlations were found between high Karnofsky scores and specific SF-36 components, including Physical Functioning, Role Physical, and Social Functioning, suggesting that these aspects critically influence overall QOL. Notably, no correlation was identified between age and KPSS, highlighting that disease severity rather than age impacts QOL. Findings underscore the complementary roles of KPSS and SF-36 in assessing QOL in terminally ill patients; while some measures in SF-36 aligned closely with KPSS, others offered essential insights into patient experiences. This comprehensive approach emphasizes the need for robust QOL evaluations in palliative care, facilitating more patient-centered care aligned with individuals' values and needs.