ICAM1 antibody‐bound ICG triggers tumor‐specific, caspase‐1‐independent pyroptosis via CTSS‐mediated GSDMD cleavage, activates antitumor immunity, and synergizes with anti–PD‐1 therapy, offering a non‐apoptotic strategy to overcome resistance in cancer treatment. The gene discussed is CTSS; the disease is neoplasm.