The　complexity,　variability,　and　heterogeneity　of　the　tumor　microenvironment　make　it　impossible　for　monotherapy　to　achieve　the　desired　therapeutic　effect.　The　utilization　of　nanoreactor-based　multimodal　synergistic　therapy　represents　a　highly　promising　approach.　Consequently,　we　utilized　metal　coordination-constructed　metal-phenolic　networks　(MPNs)　to　encapsulate　glucose　oxidase　(GOx),　which　then　co-assembled　with　indocyanine　green　(ICG),　ultimately　forming　a　cascade　nanoreactor　(GOx@TF-ICG　NPs)　that　exhibits　a　multimodal　synergistic　therapeutic　effect.　As　a　simple　and　efficient　nanoreactor,　it　initiates　a　cascade　reaction　by　GOx　and　achieves　multimodal　synergistic　anti-tumor.　After　entering　the　tumor　microenvironment,　the　nanoreactor　catalyzes　glucose　to　produce　hydrogen　peroxide　(H2O2),　initiating　a　cascade　that　triggers　a　reactive　oxygen　species　(ROS)　storm,　enhancing　chemodynamic　therapy　(CDT)　and　photodynamic　therapy　(PDT),　ultimately　inducing　ferroptosis.　The　photothermal　effect　directly　initiated　by　the　coordination　structure　of　MPNs　and　ICG,　together　with　the　down-regulation　of　heat　shock　proteins,　jointly　strengthens　the　photothermal　therapy　(PTT)　effect.　The　experimental　results　show　that　the　nanoreactor　can　also　induce　tumor　cell　apoptosis　by　decreasing　the　mitochondrial　membrane　potential.　Therefore,　the　nanoreactor　integrates　starvation　therapy　(ST)/PDT/PTT/ferroptosis　and　has　a　significant　anti-tumor　effect.　This　strategy　provides　ideas　and　theoretical　guidance　for　combination　therapy　in　improving　the　clinical　treatment　effect　of　tumors.　©　2025　Elsevier　Ltd