Constructing a synergistic multiple-modal antibacterial platform for multi-drug-resistant (MDR) bacterial eradication and effective treatment of infected wounds remains an important and challenging goal. Herein, we developed a multifunctional Cu/Mn dual single-atom nanozyme (Cu/Mn-DSAzymes)-based synergistic mild photothermal/nanocatalytic-therapy for a MDR bacterium-infected wound. Cu/Mn-DSAzymes with collaborative effects exhibit remarkable dual CAT-like and OXD-like enzyme activities and could efficiently catalyze cascade enzymatic reactions with a low level of HO as an initial reactant to produce reparative O and lethal ˙O. Moreover, a black N-doped carbon nanosheet supports of Cu/Mn-DSAzymes show superior NIR-II-triggered photothermal performance, endowing them with photothermal-enhanced dual enzyme catalysis. In addition, such enhanced dual enzyme catalysis likely improves the susceptibility and lethality of photothermal effects on MDR bacteria. and studies demonstrate that Cu/Mn-DSAzyme-mediated synergistic nanocatalytic and photothermal effects possess dramatic antibacterial outcomes against MDR bacteria and evidently reduced inflammation at wound sites. Moreover, the combined photothermal effect and O release mediated by Cu/Mn-DSAzymes promotes macrophage polarization to reparative M2 phenotype, collagen deposition, and angiogenesis, considerably accelerating wound healing. Therefore, Cu/Mn-DSAzyme-based synergetic dual-modal antibacterial therapy is a promising strategy for MDR bacterium-infected wound treatment, owing to their excellent antibacterial ability and significant tissue remodeling effects.