Although they enhance antitumor T cell activity, STING agonists also elicit protumorigenic effects by promoting IL‐35‐producing B regulatory (Breg) cells, suppressing natural killer (NK) cell density, and fostering immune suppression. To address these challenges, this work develops a tumor microenvironment‐responsive hollow mesoporous nanosystem that degrades under high glutathione conditions, thereby releasing the STING agonist MSA‐2 and Mn ions. Here, STING1 is linked to neoplasm.