Background: Prehabilitation seeks to optimize patient health before surgery to improve outcomes. Randomized controlled trials (RCTs) have been conducted on prehabilitation, however an updated synthesis of this evidence is required across General Surgery to inform potential Supplementary discipline-level protocols. Accordingly, this systematic review of RCTs aimed to evaluate the use of prehabilitation interventions across the discipline of General Surgery. Methods: This study was registered with PROSPERO (CRD42023403289), and adhered to PRISMA 2020 and SWiM guidelines. PubMed/MEDLINE and Ovid Embase were searched to 4 March 2023 for RCTs evaluating prehabilitation interventions within the discipline of General Surgery. After data extraction, risk of bias was assessed using the Cochrane RoB 2 tool. Quantitative and qualitative data were synthesized and analysed. However, meta-analysis was precluded due to heterogeneity across included studies. Results: From 929 records, 36 RCTs of mostly low risk of bias were included. 17 (47.2%) were from Europe, and 14 (38.9%) North America. 30 (83.3%) investigated cancer populations. 31 (86.1%) investigated physical interventions, finding no significant difference in 16 (51.6%) and significant improvement in 14 (45.2%). Nine (25%) investigated psychological interventions: six (66.7%) found significant improvement, three (33.3%) found no significant difference. Five (13.9%) investigated nutritional interventions, finding no significant difference in three (60%), and significant improvement in two (40%). Conclusions: Prehabilitation interventions showed mixed levels of effectiveness, and there is insufficient RCT evidence to suggest system-level delivery across General Surgery within standardized protocols. However, given potential benefits and non-inferiority to standard care, they should be considered on a case-by-case basis.