Due to repeated microbial infection and immunosuppressive microenvironment, chronic wound healing was significantly hindered. The development of multifunctional nanomaterials capable of simultaneously antibacterial and immunomodulatory continue to present challenges. Herein, a multifunctional nanocomposite, MXene/Cu2-xO, was developed that integrates photothermal therapy (PTT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT) tri-modal therapy for synergistic antibacterial and immunomodulation wound healing. MXene/Cu2-xO exhibited remarkable reactive oxygen species (ROS) generation through Fenton-like reaction and ultrasound (US)-triggered in situ TiO2 sensitization. In response to weakly acidic infection microenvironment, the prepared nanocomposite could achieve robust antibacterial and anti-biofilm efficacy under near infrared light (NIR) and US irradiation via synergistic ROS and hyperthermia. Concurrently, macrophages could be polarized toward the pro-inflammatory M1 phenotype, augmenting bactericidal activity with inflammatory factor secretion regulated. Additionally, hypoxia-inducible factor (HIF-1α)/vascular endothelial growth factor (VEGF)-driven angiogenesis was significantly promoted. Thus, MXene/Cu2-xO markedly accelerated wound healing under NIR/US irradiation. Both in vitro and in vivo research results confirmed that MXene/Cu2-xO exhibits excellent antibacterial and immunomodulatory capability, and can effectively expedite infected wound healing. This work presents a paradigm of multimodal synergistic therapy in wound healing, offering inspiration for advancing chronic refractory wound treatment.