Background: Although exercise has been widely established as an efficacious rehabilitative therapy for cancer survivors in rigorously designed research studies, demonstration of translation of this research into clinical oncology practice is needed. The purpose of this study was to evaluate the effectiveness of a real-world cancer rehabilitation program implemented within a healthcare setting. Patients and Methods: This study involved 299 adult cancer survivors enrolled in a hospital-based, supervised, individualized, cancer rehabilitation program. A retrospective review of the 132 participants who completed the follow-up assessment was performed. Sixty-minute sessions consisting of aerobic, resistance, flexibility, and relaxation exercises were performed twice weekly. Questionnaires and fitness assessments were administered at enrollment and after 24 sessions by exercise physiologists. Change in a number of health-related physical fitness and patient-reported outcomes and the influence of baseline characteristics on program outcomes were assessed. Results: There were no baseline differences between those who completed the follow-up assessment and those who withdrew. Statistically and/or clinically meaningful improvements occurred in functional capacity, blood pressure, muscular endurance, flexibility, health-related quality of life, and fatigue, but not in body composition. Age, marital status, radiation treatment status, exercise frequency before diagnosis, smoking status, and alcohol consumption frequency influenced functional capacity and/or quality-of-life changes. Conclusions: Adoption of cancer rehabilitation as a standard part of oncology care may improve cancer survivors' health and well-being.