BACKGROUND: Exercise can help mitigate side effects of hematopoietic stem cell transplantation (HSCT), particularly when initiated before HSCT. However, the exercise-related barriers, facilitators, and preferences of this population remain unclear. OBJECTIVE: This study aimed to explore the patient experience to inform future implementation of a prehabilitation intervention. INTERVENTIONS/METHODS: A 2-phase sequential explanatory mixed-methods study was conducted using (1) cross-sectional survey and (2) focus groups. Survey questions aligned with the Theoretical Domains Framework. Focus group data were analyzed using a directed content analysis approach, followed by inductive thematic analysis to generate themes that represented the exercise-related barriers, facilitators, and preferences of participants. RESULTS: Twenty-six participants completed phase 1 (n = 22 with multiple myeloma). Fifty percent of participants (n = 13) were fairly/very confident in their ability to exercise pre-HSCT. Eleven participants completed phase 2. Exercise barriers included knowledge/skill limitations, inadequate healthcare provider support, and the emotional toll of treatment. Facilitators included social support and goals. Exercise preferences were related to 2 themes: (1) program structure (subthemes: prescription and scheduling, mode of delivery) and (2) support (subthemes: support from personnel, tailoring, and education). CONCLUSION: Key exercise-related barriers included knowledge limitations, disease/treatment effects, and inadequate support. Prehabilitation should be tailored, flexible, and include education and a virtual or hybrid delivery model in this population. IMPLICATIONS FOR PRACTICE: Nurses are well positioned to identify functional limitations and counsel and refer patients to exercise programming and/or physiotherapy services. Including an exercise professional in the pretransplant care team would provide key supportive care assistance for the nursing team.