The current literature describes a variety of techniques detailed under the name of combined endoscopic-laparoscopic surgery (CELS) procedures. This systematic review of literature assessed the outcomes of colonoscopic-assisted laparoscopic-wedge resection (CAL-WR) in particular to evaluate its feasibility to remove colonic lesions that do not qualify for endoscopic resection. Electronic databases (PubMed, Embase, and Cochrane) were searched for studies evaluating CAL-WR for the treatment of colonic lesions. Studies with missing full text, language other than English, systematic reviews, and studies with fewer than ten patients were excluded. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Out of 68 results, duplicate studies (n = 27) as well as studies that did not meet the inclusion criteria (n = 32) were removed. Nine studies were included, encompassing 326 patients who underwent a CAL-WR of the colon. The technical success rate varied from 93 to 100%, with an R0 resection rate of 91–100%. Morbidity ranged from 6% to 20%. The quality of the included studies was rated as low to moderate and contained heterogeneous terminology, methodology, and outcome measures. There is insufficient high-quality data and substantial variation in outcome measures to draw firm conclusions regarding the value of CAL-WR. Although CAL-WR is a promising local resection technique for endoscopically unremovable neoplasms of the colon, further investigation of this technique in well-designed prospective, multicenter studies with predefined outcome measures is required. Trial registration: A protocol for this systematic review was registered in PROSPERO with the number CRD42023407966. [ABSTRACT FROM AUTHOR]