Introduction: Tumor-based molecular profiling has increased in the area of precision medicine. Their routine use is still limited by accessibility, cost and availability of tumor material. Materials and Methods: We retrospectively analysed the treatment received and the survival data of patients with digestive cancer who received molecular high-throughput sequencing (NGS) analyses at diagnosis. The primary objective of this single-center study was to compare the overall survival of patients who were treated with molecularly matched therapy with patients who received standard therapy. Median overall survival was calculated from initial disease diagnosis to death. Results: 528 patients were referred to the Digestive Oncology Department of the Timone Hospital in Marseille between January 2018, and November 2020 for management of digestive cancer and received high-throughput molecular sequencing. Among them, 461 patients had a digestive carcinoma (75 of them were excluded because of the presence of a GIST or a neuroendocrine tumor, a digestive localization of extra digestive cancer or the absence of follow-up in our center) and 275 had metastatic disease (synchronous or metachronous). For metastatic patients, actionable molecular alterations were identified in95 patients (43.5%) and for 13 patients (4.7%) a molecularly matched therapy was administered. There was no significant difference in median overall survival between patients who received matched therapy than patients who did not receive molecularly matched therapy (2.89 [95%CI 1.84-3.93] vs. 2.86 [95%CI 1.52-4.19], p=0.671). Conclusion: This study suggests that high-throughput genomics can improve management of patients. Although these results did not show a benefit in overall survival for tumors who harboured such actionable molecular alterations and who received molecularly matched therapy, than patients who did not receive molecularly matched therapy, they are promising. Randomized trials are needed to confirm that there is a benefit to treating patients with matched therapy based on NGS.