The design of multifunctional nanoplatforms is of great importance for improving hypoxia-induced therapeutic outcomes, especially for overcoming radiotherapy (RT) tolerance. Here, two-dimensional intermetallic PtBi/Pt nanoplates (PtBi NPs) were designed as a therapeutic platform to in situ generate oxygen, and thereby overcome tumor hypoxia for boosting photothermal/radiotherapy (PTT/RT). With high X-ray attenuation coefficient, PtBi NPs exhibited outstanding radiotherapy sensitization characteristics. Moreover, the high photothermal effect of PtBi NPs could promote the catalytic activity of PtBi NPs to achieve a synergistic PTT/RT effect. PEGylated PtBi NPs (PtBi-PEG) exhibited excellent biocompatibility, prolonged blood circulation time and enhanced tumor accumulation. Finally, PtBi-PEG showed excellent trimodal contrast enhancement for infrared (IR) imaging, photoacoustic (PA) imaging and X-ray imaging, facilitating imaging-guided cancer therapy. Thus, our work highlights PtBi-PEG as a novel multifunctional theranostic nanoplatform with great potential for future multimodal imaging-guided synergistic cancer therapy.