The Front Cover shows the synthesis, subcellular localization, and anticancer action mechanism of two novel unsymmetrical Ir(III) complexes, Ir1 and Ir2. Ir1 is mainly located in mitochondria. In contrast, Ir2 accumulates in mitochondria but subsequently migrates to the nucleus. Ir1 and Ir2 showed cytotoxicity toward cancerous cells, especially the cisplatin‐resistant ones. Although both Ir1 and Ir2 disrupted the mitochondrial metabolism, they showed different cell death mechanisms. Ir1 induced mitochondria‐mediated apoptosis in cisplatin‐resistant A549R cells. Ir2 was demonstrated to cause PARP‐1 activated necroptosis in A549R cells. This study provides an experimental basis for the rational design of metal‐based chemotherapeutic drugs. More information can be found in the Research Article by Y. Chen, J. Long, H. Chao and co‐workers.