PURPOSE: This study aims to assess changes in quality of life (QoL) experienced by patients undergoing hyperthermic intravesical chemotherapy (HIVEC), using validated EORTC QLQ-C30 and EORTC QLQ-NMIBC24 questionnaires. METHODS: Between 2021 and 2024, 67 patients with high-risk non-muscle-invasive bladder cancer (NMIBC) who experienced BCG failure or intolerance were enrolled in an HIVEC regimen at our institution. Functional outcomes were evaluated through the EORTC QLQ-C30 and EORTC QLQ-NMIBC24 questionnaires administered at baseline (prior to treatment), after six weekly instillations (induction phase), after three monthly instillations (3 months), and after an additional six monthly instillations (9 months). Each response was assigned a specific score to assess QoL variations over time. RESULTS: Of the 67 patients enrolled, 13 discontinued the therapy. After 9 months, 54 patients completed the EORTC QLQ-C30 and NMIBC24 questionnaires. The QLQ-C30 results indicate that the therapy did not significantly affect daily activities, despite reported increases in fatigue and weakness. However, negative impacts were observed in terms of pain, concentration, and engagement in recreational activities, alongside growing concerns about disease recurrence. The NMIBC24 questionnaire revealed an increase in urinary frequency, associated insomnia, and discomfort related to catheter use. Additionally, there was a decline in libido and anxiety about contaminating their partners. CONCLUSIONS: While the initial phase of HIVEC therapy significantly impacts QoL, particularly regarding pain and psychological concerns, it does not drastically affect daily activities in the long term. Nevertheless, the treatment has a negative influence on both physical and mental well-being, contributing to increased anxiety and limitations in social and recreational activities, as well as reduced sexual function.