In this study, we prepared a GSH‐responsive degradable mesoporous silica nanoformulation (dMSN‐SB) that inhibited TGF‐β signaling within the tumor microenvironment, promoted TAN polarization toward the anti‐tumor N1 phenotype, enhanced pancreatic cancer response to combined IRE and αPD1 therapy, and induced long‐term antitumor memory. The gene discussed is TGFB1; the disease is familial pancreatic carcinoma.