Chemodynamic therapy (CDT), which suppresses tumors via the conversion of endogenous hydrogen peroxide (HO) to highly toxic hydroxyl radicals (•OH), is deemed as a cutting-edge antitumor strategy. However, the insufficient endogenous HO and up-regulated antioxidant glutathione (GSH) in the tumor microenvironment (TME) greatly impede the therapeutic effect of CDT. Herein, a versatile nanoplatform MgO@SnFeO@PEG (MSnFeP) is elaborately fabricated for boosting CDT synergetic phototherapy. In the TME, the activation of MSnFeP contributes to in situ supply of HO, generation of •OH and consumption of GSH for boosted CDT. Furthermore, photothermal therapy (PTT) and photodynamic therapy (PDT) are simultaneously stimulated by near-infrared (NIR) light exposure on MSnFeP to increase the toxic free radical yield. This strategy not only amplifies the CDT efficacy hindered by HO deficiency and GSH overexpression, but also further enhances the therapeutic effect with the combination of phototherapy.