ABSTRACTThe emergence of bacterial resistance has a negative impact on the conventional antimicrobial treatments, and research into the development of the new antimicrobial materials is of great significance. Multimodal synergistic antimicrobial materials exert better antimicrobial effects compared with a single modality. In recent years, Polyoxometalate (POM) has shown great potential in the biomedical field due to its high catalytic activity and high photothermal conversion ability. However, owing to its small surface area, its applications have been greatly limited. Herein, we designed a H2O2 self‐supplied CDT and PTT bimodal nanogeneration material (i.e., CaO2/POM@MOF) possessing a larger surface area for the treatment of the bacterial infections, in which CaO2 could release O2 and H2O2 in the weakly acidic microenvironment of bacterial infection and the dual catalytic site of POM@MOF could enhance the CDT reaction to generate ROS, resulting in the bacterial oxidative stress and the leakage of the bacterial contents, and the exposure to the NIR light generates localized high temperature that cause the rupture of bacterial cell membranes and the denaturation of their proteins. Meanwhile, the superior stability of POM@MOF can release fewer metal ions to improve its biocompatibility. The in vitro antimicrobial experiments demonstrated that CaO2/POM@MOF possessed the combined CDT and PTT effect and exhibited excellent antimicrobial efficacy. This work presents a promising strategy to combat the bacterial infections.