AbstractMultifunctional heterostructures fabricated by assembling individual components are identified as a potential theranostic tool in biological fields, representing a strategy of great significance. Herein, heterodimers of the zeolitic imidazolate framework (ZIF)‐8 and gold nanorods (Au NRs) are designed and synthesized for collaborative photothermal treatment and chemotherapy triggered by near‐infrared (NIR) light. Furthermore, Ag2S, Ag2Se, upconversion fluorescent nanoparticles, and doxorubicin hydrochloride loaded into the ZIF‐8 are released after intravenous injection. This release is attributed to the pH‐responsive system, which simultaneously enabled computed tomography, photoacoustic, and NIR fluorescence imaging for tumors. Under NIR irradiation using an 808 nm laser, the tumor can be completely eliminated in vivo through multimodal imaging‐guided chemophotothermal treatment. Overall, the present study makes several noteworthy contributions to the efficient diagnosis and treatment of cancer using the metal‐organic framework‐assisted heterodimer as a versatile nanoplatform.