Although synergistic therapy for tumors has displayed significant promise for effective treatment of cancer, developing a simple and effective strategy to build a multi-functional nanoplatform is still a huge challenge. By virtue of the characteristics of tumor microenvironment, such as hypoxia, slight acidity and H2O2 overexpression, Au2Pt-PEG-Ce6 nanoformulation is constructed for collaborative chemodynamic/phototherapy of tumors. Specifically, the Au2Pt nanozymes with multiple functions are synthesized in one step at room temperature. The photosensitizer chlorin e6 (Ce6) is covalently linked to Au2Pt nanozymes for photodynamic therapy (PDT). Interestingly, the Au2Pt nanozymes possess catalase- and peroxidase-like activities simultaneously, which not only can generate O2 for relaxation of tumor hypoxia and enhancement of PDT efficiency but also can produce ∙OH for chemodynamic therapy (CDT). In addition, the high photothermal conversion efficiency (η = 31.5%) of Au2Pt-PEG-Ce6 nanoformulation provides the possibility for photoacoustic (PA) and photothermal (PT) imaging guided photothermal therapy (PTT). Moreover, the presence of high-Z elements (Au and Pt) in Au2Pt-PEG-Ce6 nanoformulation endows it with the ability to act as an X-ray computed tomography (CT) imaging contrast agent. All in all, the Au2Pt-PEG-Ce6 exhibits great potential in multimodal imaging-guided synergistic PTT/PDT/CDT with remarkably tumor specificity and enhanced therapy.