Abstract Porous metal–organic frameworks (MOFs) nanostructures constructed from metal ion/ion clusters and organic bridging ligands hold great promise for biomedicine applications. The developing of nanoagents achieving accurate diagnosis and improved therapeutic effect is highly desirable. Herein, a new‐style versatile zirconium‐ferriporphyrin metal–organic framework (Zr‐FeP MOF) nanoshuttles is reported using a facile one‐pot hydrothermal method. The Zr‐FeP MOF nanoshuttles enable simultaneously to generate abundant reactive oxygen species including hydroxyl radical (·OH) and singlet oxygen ( 1 O 2 ) under a near‐infrared (NIR) laser irradiation. Significant photothermal effect of Zr‐FeP MOF nanoshuttles with photothermal conversion efficiency high to 33.7% is also demonstrated. Under a single NIR laser irradiation, the Zr‐FeP MOF nanoshuttles loaded with heat shock protein 70 siRNA efficiently suppress the tumor growth both in vitro and in vivo owing to the synergistic effect of photodynamic therapy (PDT) and low‐temperature photothermal therapy (PTT). Meanwhile, it exhibits good photothermal imaging, computed tomography, and photoacoustic imaging tri‐mode tumor‐specific imaging capability for tumor accurate diagnosis. This work contributes to design “all‐in‐one” nanoagents that realize multimodal imaging diagnosis and PDT and low‐temperature PTT synergistic treatments.

Metal–Organic Framework Nanoshuttle for Synergistic Photodynamic and Low‐Temperature Photothermal Therapy