Catalytic　tumor　therapy　based　on　two-dimensional　(2D)　nanomaterials　is　a　burgeoning　and　promising　tumor　therapeutic　modality.　However,　the　inefficient　utilization　and　conversion　of　exogenous　stimulation,　single　catalytic　modality,　and　unsatisfactory　therapeutic　efficiency　in　the　tumor　microenvironment　(TME)　have　seriously　restricted　their　further　application　in　tumor　therapy.　Herein,　the　heterogeneous　carbon　nitride-based　nanoagent　named　T-HCN@CuMS　was　successfully　developed,　which　dramatically　improved　the　efficiency　of　the　tumor　therapeutic　modality.　Benefiting　from　the　donor-acceptor　(triazine-heptazine)　structure　within　the　heterogeneous　carbon　nitride　nanosheets　(HCN)　and　the　construction　of　interplanar　heterostructure　with　copper　loaded　metallic　molybdenum　bisulfide　nanosheets　(CuMS),　T-HCN@CuMS　presented　a　favorable　photo-induced　catalytic　property　to　generate　abundant　reactive　oxygen　species　(ROS)　under　near-infrared　(NIR)　light　irradiation.　Besides,　the　choice　of　CuMS　simultaneously　enabled　this　nanoagent　to　efficiently　catalyze　the　Fenton-like　reaction　and　trigger　cell　cuproptosis,　a　recently　recognized　regulated　cell　death　mode　characterized　by　imbalanced　intracellular　copper　homeostasis　and　aggregation　of　lipoylated　mitochondrial　proteins.　Moreover,　upon　surface　modification　with　cRGDfk-PEG2k-DSPE,　T-HCN@CuMS　was　prepared　and　endowed　with　improved　dispersibility　and　αvβ3　integrins　targeting　ability.　In　general,　through　the　rational　design,　T-HCN@CuMS　was　facilely　prepared　and　had　achieved　satisfactory　antitumor　and　antimetastasis　outcomes　both　in　vitro　and　in　a　high-metastatic　orthotopic　osteosarcoma　model.　This　strategy　could　offer　an　idea　to　treat　malignant　diseases　based　on　2D　nanomaterials.　©　2023　American　Chemical　Society.