BACKGROUND: Due to the lack of available knowledge in the current literature, this systematic review and meta-analysis was aimed to assess the effectiveness of exercise-based lifestyle interventions, including healthy diet and/or psychological well-being on mental, physical and global health-related quality of life (HRQoL) in adults after cancer treatment. METHODS: MEDLINE (via PubMed) and Web of Science databases were searched for randomised controlled trials (RCTs) published until August 2024 evaluating exercise-based lifestyle interventions, including healthy diet and/or psychological well-being, which assessed mental, physical and global HRQoL. RESULTS: Of 6193 screened studies, 32 RCTs met the criteria. The total sample comprised 5528 participants (3003 intervention and 2525 control). There was a small effect size in a pooled analysis that found exercise-based lifestyle interventions improve mental HRQoL (d 0.11, 95% CI 0.05 to 0.18). These effects were greater in those studies that combined exercise with psychological well-being (d 0.19, p = 0.004), and with moderate-to-high intensity aerobic exercise (moderate intensity; d 0.11, p = 0.02, high intensity; d 0.16, p = 0.02, aerobic exercise; d 0.16, p = 0.26). CONCLUSIONS: Exercise-based lifestyle interventions do not enhance physical nor global HRQoL, yet those combined with psychological well-being seem to improve mental HRQoL in individuals after cancer treatment. PROSPERO REGISTRATION NUMBER: CRD42022369169.

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