Background and Objectives Outcomes for gastrointestinal peritoneal metastases (GI‐PM) are worse compared to systemic metastases, with a paucity of data exploring extended mutation profiling. An exploratory mutation analysis in GI‐PMs was performed as a “proof of concept” of potential predictive values of profiling in GI‐PM and rates of actionable mutations. Methods The study included 40 GI‐PM patients: 14 low‐grade mucinous carcinoma peritonei and 26 HG‐PM (12 colons, 10 appendix, 4 small bowels). Demographics, histologies, peritoneal cancer indexes, cytoreduction scores, and survival data were collected. NGS 50‐gene mutation profiling was performed on 38 specimens. The association of mutations with survival was evaluated in high‐grade PM. Results KRAS, TP53, and SMAD4 mutations were observed in 61%, 29%, and 8% of cases across all tumor histologies. In 66% cases >1 mutations occurred, associated with decreased survival in HG‐PM: 32 vs 73 months, P = .03. TP53 or SMAD4 mutations were associated with decreased survival in HG‐PM: 22 vs 48 months, P = .02. Actionable mutations were detected in 70%. Conclusion Actionable mutations were detected at high rates. GI‐PMs have similar mutational profiles and TP53, SMAD4, and/or >1 mutation were associate with decreased survival in HG‐PM. This data supports the concept of the extended mutation profiling utility in GI‐PM warranting further investigation.