These findings indicated that the NM@PLGA‐MTI‐OXA nanodrug reverses the Fn‐mediated immunosuppressive microenvironment, increases cytotoxic CD8+ and CD4+ T cell infiltration, effectively reduces inflammatory cytokine expression in the colorectal cancer mouse model, and enhances the efficacy of the chemotherapeutic agent oxaliplatin after clearing intratumoral bacteria. Here, CD8A is linked to colorectal cancer.