Cancer survivors (CS) often experience treatment-related side effects, such as fatigue, and have reduced physical function. Regular physical activity has been demonstrated to reduce these symptoms and improve cardiopulmonary fitness. Digital solutions are needed to optimize exercise options for CS in aftercare, especially given the significant limitations during the Covid-19 pandemic. This two-armed, non-randomized, controlled intervention study for CS aims to investigate whether a telemedicine-based exercise intervention is as effective as the current standard of care for oncological exercise therapy in aftercare. Patients in the intervention group (n = 61) performed a telemedicine-based exercise program (TE) and patients in the control group (n = 31) participated in an existing rehabilitation sports group (RG) over a six-month intervention period. The primary outcome was cardiopulmonary fitness measured by VO2peak; secondary outcomes included quality of life (QoL), fatigue, and physical activity. A non-inferiority analysis was performed with a predefined non-inferiority margin for relative VO2peak of -1.50 ml/min/kg. Although TE demonstrated a slight advantage in relative VO2peak compared to RG (adjusted mean difference of 0.55 ml/min/kg [95% CI: -2.74; 3.84]), the non-inferiority was not statistically significant. Nevertheless, the implementation of a telemedicine-based exercise intervention indicates that individual patients respond well to this type of exercise program and benefit from the intervention, particularly in terms of QoL. Finding an individualized program for each cancer survivor is the overarching goal. A telemedicine-based exercise intervention may be a promising option, particularly for younger patients.