Impressively, US-stimulated Mn-MOF not only induced dual apoptosis/ferroptosis but also enhanced the antitumor immunity response by improving the numbers of mature dendritic cells and activated CD8+ T cells and reducing the numbers of myeloid-derived suppressor cells (MDSCs) in H22 primary liver and 4T1 metastatic breast tumor models, thus showing its great potential as an advanced smart SDT nanosystem to achieve efficient suppression of hypoxic tumors. Here, CD8A is linked to breast neoplasm.