Background: Decision-making regarding palliative treatment for patients with metastatic colorectal cancer (mCRC) is complex and comprises numerous decisions. Decision-making should be guided by the premise of maintaining and/or improving patients' quality of life, by patient preference, and by the trade-off between treatment benefits and harm. Decision support systems (DSSs) for clinicians (eg, nomograms) can assist in this process. The present systematic review aimed to provide a comprehensive overview of the available DSSs for incurable mCRC and to assess their clinical usefulness. Materials and Methods: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library. We extracted information on the DSS characteristics and their discriminatory ability, calibration, and user-friendliness. Results: From 5205 studies, we identified 14 DSSs for decisions regarding palliative resection of the primary tumor (n = 3), radiotherapy for metastases (n = 2), treatment type (invasive vs. symptomatic only; n = 7), and selection of chemotherapy (n = 2). The predictors varied greatly among the DSSs, and only 1 DSS incorporated a genetic marker (ie, UGT1A1). None of the DSSs included > 1 treatment option, nor did any DSS present estimates of treatment benefits and harms. Five tools had not been externally validated, two had only been validated in < 35 patients, and the rest had only been validated in populations similar to the population used for their development. Discriminatory accuracy was generally moderate to poor. Calibration measures were only reported for 2 tools. Conclusion: A limited number of DSSs are available to support palliative treatment decisions for patients with mCRC, and the evidence regarding their discriminatory ability and calibration is too limited to recommend their use. New DSSs comparing multiple treatment options and presenting both treatment benefits and harms are needed.