Traditional combination therapy of photodynamic therapy (PDT) and photothermal therapy (PTT) is limited in the field of clinical cancer therapy due to activation by light with separate wavelengths, insufficient O2 supply, antioxidant ability of glutathione (GSH) in tumor cell, and low penetration depth of light. Here, a multifunctional nanoplatform composed of MoO3-x nanosheets, Ag nanocubes, and MnO2 nanoparticles was developed to overcome these drawbacks. For this nanoplatform, hyperthermia and reactive oxygen species (ROS) were simultaneously generated under single 808 nm near-infrared (NIR) light irradiation. Once this nanoplatform accumulated in the tumor region, GSH was depleted by MnO2 and intracellular H2O2 was catalyzed by MnO2 to produce O2 to relieve hypoxia. Ultrasound (US) imaging confirmed in-situ O2 generation. Magnetic resonance (MR) imaging, photoacoustic (PA) imaging, and fluorescence imaging were used to monitor in vivo biodistribution of nanomaterials. This provides a paradigm to rationally design a single NIR laser induced multimodal imaging-guided efficient PDT/PTT cancer strategy.