Purpose <p>This study evaluates the feasibility of a comprehensive supervised exercise program (CSEP) for head and neck cancer (HNC) patients during and after (chemo)radiotherapy, integrating quantitative and qualitative data to identify participation barriers and facilitators.</p> Methods <p>To investigate the feasibility of the CSEP, a mixed-method study was performed. For the quantitative part, first, adherence to and safety of the CSEP were considered as quantitative feasibility outcome measures. Second, two questionnaires evaluated acceptability, adherence, feasibility, therapeutic support, and overall evaluation at 12 weeks and 6 months after the start of the radiotherapy. Additionally, focus groups were held to discuss acceptability, adherence, expectations, feasibility, therapeutic support, and overall evaluation. The quantitative and qualitative data were integrated and discussed via a joint display table.</p> Results <p>Quantitative data were available from 32 participants. Three focus groups with in total 11 participants were organized. Overall adherence to the CSEP was 72%, and no serious adverse events were reported, confirming the program’s safety. Adherence and feasibility posed challenges; hospital sessions had higher adherence due to better motivation and guidance, whereas home sessions faced issues like lack of motivation and time constraints. Participants highlighted the program’s individualization as a significant strength.</p> Conclusion <p>The CSEP was positively received, deemed safe, and feasible during and after HNC treatment, with participants recommending it to other HNC patients.</p> Trial registration <p>Trial Registration: ClinicalTrials.gov Identifier: NCT05256238 (Registered on February 25, 2022).</p>