Background There is uncertainty about whether cytoreductive surgery (CRS) + hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared to standard of care (SoC) in people with peritoneal metastases who can withstand major surgery. Primary objectives To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian, or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis. Secondary objectives To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services (PSS) perspective using a model-based cost-utility analysis. Methods We will perform a systematic review of literature by updating the searches from MEDLINE, EMBASE, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials (RCTs) comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of how CRS+HIPEC and SoC were performed, how long people were followed-up, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications, and resource utilisation data by contacting the study authors and obtaining data at the individual participant level. Using individual participant data (IPD), we will perform a two-step IPD, i.e. calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses and metaregression to investigate potential sources of heterogeneity and identify whether a subset of participants benefits from CRS+HIPEC and perform sensitivity analyses to test the robustness of results to assumptions. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting.