<p>Infected wounds present a high clinical incidence, and current treatments are inadequate in both effectively eliminating bacterial biofilms and continuously promoting tissue regeneration. To address these challenges, we develop a microwave-responsive thermoelectric nanocomposite of zinc oxide-bismuth telluride (ZnO-Bi₂Te₃) via hydrothermal synthesis for the treatment of biofilm infected wounds. The heterointerface within the nanocomposite enhances phonon scattering, while the ZnO component provides additional charge carrier transport pathways, collectively significantly improving the thermoelectric conversion performance. Under microwave irradiation, the ZnO-Bi₂Te₃ rapidly generates substantial amounts of reactive oxygen species (ROS), enabling efficient penetration and eradication of biofilms with an antibacterial rate of 99.2%. After irradiation ceases, the ZnO-Bi₂Te₃ utilizes the wound-environment temperature difference to continuously produce thermoelectric signals. The continuous thermoelectric signals, in synergy with the release of zinc ions, activate the MAPK pathway and promote protein synthesis, processing, and transport, thereby enhancing cell migration, differentiation, and angiogenesis, leading to continuous tissue regeneration. In a mouse model of MRSA-biofilm infected wounds, the ZnO-Bi₂Te₃ loaded microneedles effectively clear the infection and accelerate healing. This study develops a microwave-responsive thermoelectric system for infected wounds through efficient biofilm clearance and sustained pro-regeneration.</p> Graphical Abstract <p></p>