Given the potent antitumour effects of OMVs, this study systematically evaluated the efficacy and mechanistic basis of modified OMVs derived from engineered E. coli MG1655 in CDH17‐positive colorectal (CRC) and pancreatic ductal adenocarcinoma (PDAC) models. The gene discussed is CDH17; the disease is pancreatic ductal adenocarcinoma.