Oxygen deficiency is a major obstacle to hypoxic-related cancer theranostics, and developing the oxygen production nanoplatforms received the widespread attention. However, it is remaining a challenge to structure a nanoplatform with hypoxia alleviation effect and imaging-guided cancer radiotherapy. Herein, we present a novel theranostics nanoplatform (Au NPs/UCNPs/WO₃@C) comprising of tungsten trioxide (WO₃) that loaded gold nanoparticles (Au NPs) and up-conversion nanoparticles (UCNPs) for improved photoacoustic (PA) imaging performance in the second near infrared window (NIR-II, 900–1,700 nm). Au NPs/UCNPs/WO₃@C exhibited superior oxygen-generation effect and doxorubicin loading capacity, thus serving as an efficient radiosensitizer for radio-chemo anti-cancer therapy. Importantly, the accumulated Au NPs/UCNPs/WO₃@C in the tumor region led to the increased NIR-II PA imaging signal and the blood oxygen saturation signal, which could enhance radiation sensitivity and accurately guiding cancer radiotherapy to reduce side effects on normal tissues. This study with proof-of-concept confirmed the multifaceted characteristics and encouraging potential of biomimetic Au NPs/UCNPs/WO₃@C for NIR-II PA imaging-guided tumor therapeutics.