Introduction eHealth exercise interventions have the unique ability to leverage the benefits of in-person programming (tailoring and supervision) with the benefits of home programming (flexibility). There may be a role for eHealth-delivered exercise for people with multiple myeloma (MM), as exercise tailoring and supervision are critical for successful outcomes due to the significant impacts/risks of myeloma-related side effects. The purpose of this study was to determine the safety, feasibility, and preliminary efficacy of a 12-week virtually supported eHealth exercise program. Methods Participants with MM completed a 12-week virtually supported home exercise program involving virtually supervised group workouts, independent workouts, and aerobic exercise. Tailoring was facilitated by the functionality of HEAL-Me, a novel eHealth app. Participants completed virtual fitness assessments and questionnaires at baseline and week 12. Results Twenty-nine participants consented, 26 completed all follow-up testing (90%). Exercise adherence was 90% (group), 83% (independent), and 90% (aerobic). No serious adverse events (grade ≥3) occurred. Significant improvements were found for quality of life and physical fitness. There was a high level of program/app satisfaction: 96% of participants agreed or strongly agreed that the exercise program was beneficial, 93% found it enjoyable, 89% were satisfied or very satisfied with delivery through the HEAL-Me app, and 48% felt that the eHealth program helped them manage cancer-related symptoms and side-effects. Conclusion An eHealth intervention that is individually tailored and includes virtual supervision and active support from the healthcare team is feasible and acceptable to people with MM. The findings from this study warrant investigation using a large-scale randomized controlled trial.