PurposeThis study aimed to investigate the impact of nutritional status and frailty phenotype and the predictors of temporal changes on health-related quality of life (HRQoL) of patients with bladder or kidney cancer. MethodsFrailty phenotype, Patient-Generated Subjective Global Assessment, and Quality-of-life questionnaire Core-30 were applied twice to patients diagnosed with bladder or kidney cancer. Patients also completed a sociodemographic questionnaire, and clinical data were collected from records. ResultsSixty-two individuals completed the study, mostly male, with a mean age of 62.5 (+/- 11.4) years. The median time of follow-up was 14.5 months. Role functioning, emotional functioning, and fatigue improved over time (p < 0.05). The factors that negatively affected the long-term quality of life summary score were being female, malnourished, pre-frail and frail, cancer treatment, performance status, and lower income. Using the multivariate model, being malnourished (beta = - 7.25; 95% CI, - 10.78 to - 3.71; p < 0.001), frail (beta = - 7.25; 95% CI, - 13.39 to - 1.11; p = 0.021), and each one-point increase in performance status (beta = - 6.9; 95% CI, - 9.54 to - 4.26; p < 0.001), were the ones that most negatively impacted the HRQoL between the two assessments. ConclusionThis study confirmed that frailty, nutritional status, and performance status are the main predictors of HRQoL of patients with bladder or kidney cancer over time. Implications for Cancer SurvivorsThese findings may be the first step towards highlighting the importance of preventing malnutrition and frailty, in favor of a better long-term QoL for cancer patients.