Background: It is well acknowledged that the poor prognosis of gastrointestinal (GI) cancer is largely due to distant metastasis. It’s been reported previously that metastasectomy, particularly with liver metastasis in colorectal cancer patients, have survival benefit. Multidisciplinary management of distant metastatic cancer mandates the consideration of all treatment options, and in selected patients with hepatic metastasectomy can be performed with curative intent. There is no consensus on the ideal management strategy for synchronous disease. The purpose of this study was to analyze the prognostic value of metastasectomy in patients with certain GI cancers associated with isolated liver metastasis. Methods: A total of 14,204 patients who underwent primary site resection along with metastasectomy for isolated liver metastases from gastric, pancreatic, and colorectal were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2019. Patients younger than 18 years, and cases with missing information including age, gender, race, unknown stage, and unknown metastasis site were excluded. Cox-regression analysis estimated the prognostic value of metastasectomy, presented by hazard ratios (HR), among different GI cancers. Survival ratios were controlled for age, race, and gender. All analyses were performed on STATA v17. Results: Study sample included 3% of patients with gastric cancer, 4.2% with pancreatic cancer, and 92.8% were colorectal cancer patients. Incidence of metastasectomy was 19.9% among gastric cancer, 30.69% of pancreatic cancer and 25.76% of colorectal cancer patients. Cox-regression analysis demonstrated survival benefit for patients with gastric (HR 0.65, CI 0.45 - 0.94, p = 0.02), pancreatic (HR 0.51, CI 0.39 – 0.67, p < 0.001), and colorectal cancer (HR 0.58, CI 0.55 – 0.62, p < 0.001) patients undergoing metastasectomy. Conclusions: Aggressive approach with primary site resection along with metastasectomy for isolated liver metastases from gastric, pancreatic, and colorectal cancers significantly improved survival. Prospective data from evidence-based protocols is missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.