People with multiple myeloma (MM) are second only to people with lung cancer for the poorest reported health-related quality of life (HRQoL) of all cancer types. Whether exercise can improve HRQoL in MM, where bone pain and lesions are common, requires investigation. This trial aims to evaluate the efficacy of an exercise intervention compared with control on HRQoL in people with MM. Following baseline testing, people with MM (n = 60) will be randomized to an exercise (EX) or waitlist control (WT) group. EX will complete 12-weeks of supervised (24 sessions) and unsupervised (12 sessions) individualized, modular multimodal exercise training. From weeks 12–52, EX continue unsupervised training thrice weekly, with one optional supervised group-based session weekly from weeks 12–24. The WT will be asked to maintain their current activity levels for the first 12-weeks, before completing the same protocol as EX for the following 52 weeks. Primary (patient-reported HRQoL) and secondary (bone health and pain, fatigue, cardiorespiratory fitness, muscle strength, body composition, disease response, and blood biomarkers) outcomes will be assessed at baseline, 12-, 24- and 52-weeks. Adverse events, attendance, and adherence will be recorded and cost-effectiveness analysis performed. The findings will inform whether exercise should be included as part of standard myeloma care to improve the health of this unique population.