Anti-glycolysis　is　well-recognized　for　inhibition　of　tumor　proliferation.　However,　tumor　metabolic　heterogeneity　confers　great　challenges　in　the　therapeutic　efficacy　of　glycolysis　inhibitors.　Here,　a　metabolic　trapping　strategy　was　employed　to　avoid　metabolism　heterogeneity　in　tumors.　Unlike　usual　glycolysis　inhibition,　the　glycolysis　level　was　first　promoted.　Then　excessive　metabolite　of　lactate　was　transformed　into　H2O2　and　hydroxyl　radical　by　lactate　oxidase　(LOX)　and　MIL-101　(Fe)　nanoparticles　(MF).　Finally,　the　ATP　production　was　inhibited,　and　the　tumor　was　suppressed　by　the　generation　of　toxic　reactive　oxygen　species　(ROS).　We　realized　this　strategy　via　methacrylated　gelatin　(GelMA)　hydrogel　microspheres,　co-loaded　with　metformin　(MET)　and　LOX@MF.　The　results　showed　that　MET　was　completely　released　within　2　h,　followed　by　most　LOX@MF　released　within　72　h.　LOX@MF　and　MET　synergistically　suppressed　tumor　proliferation　and　angiogenesis　both　in　vitro　and　in　vivo.　Compared　with　control,　the　primary　tumor　volume　was　reduced　by　75.7　%,　and　the　average　number　of　lung　metastasis　nodules　decreased　from　15.5　to　1.0.　Regarding　the　metabolism,　higher　glycolytic　enzymes　expressions　were　observed　initially,　followed　by　lower　lactate　and　vascular　endothelial　growth　factor　(VEGF),　and　finally　elevated　ROS　levels.　Overall,　our　study　provides　new　insights　to　improve　metabolism　heterogeneity-limited　metabolic　cancer　therapy.　©　2024　The　Authors