Objectives: To synthesize existing evidence on the effects of multimodal prehabilitation interventions in men affected by prostate cancer on physical, clinical, and patient-reported outcome measures. Data Sources: A systematic review was conducted according to the PRISMA 2020 Statement Guidelines. Electronic databases (ie, Medline, Embase, CINAHL and Cochrane CENTRAL, and clinicaltrials.gov) were searched using key search terms. Articles were assessed according to prespecified eligibility criteria. Data extraction and quality appraisal was conducted. The findings were integrated in a narrative synthesis. Conclusion: Of the 5863 publications screened, 118 articles were assessed in full text and 17 studies met the prescreening eligibility criteria. There were a range of study designs that included randomized controlled clinical trials (n = 11), quasi experimental (n = 4), cohort (n = 1), and case series (n = 1), covering a total of 1739 participants. The prehabilitation interventions included physical activity, peer support, pelvic floor muscle training, diet, nurse-led prehabilitation, psychological, and prehabilitation administration of phosphodiesterase-5 inhibitors. Implications for Nursing Practice: Significant heterogeneity existed in the prehabilitation intervention programs for men affected by prostate cancer in terms of the composition, duration, method of administration, and the outcomes measured to quantify their impact. This systematic review has identified that multimodal prehabilitation interventions are an emerging area for practice and research among men affected by prostate cancer. Importantly, there has been a lack of focus on the inclusion of partners as critical companions during this distressing phase of the cancer care continuum. For the moment, all members of the multidisciplinary team caring for people affected by prostate cancer are encouraged to use the findings in this review to inform holistic models of care.