AbstractNanomaterials with photothermal combined chemodynamic therapy (PTT‐CDT) have attracted the attention of researchers owing to their excellent synergistic therapeutic effects on tumors. Thus, the preparation of multifunctional materials with higher photothermal conversion efficiency and catalytic activity can achieve better synergistic therapeutic effects for melanoma. In this study, a Cu–Zn bimetallic single‐atom (Cu/PMCS) is constructed with augmented photothermal effect and catalytic activity due to the localized surface plasmon resonance (LSPR) effect. Density functional theory calculations confirmed that the enhanced photothermal effect of Cu/PMCS is due to the appearance of a new d‐orbital transition with strong spin‐orbit coupling and the induced LSPR. Additionally, Cu/PMCS exhibited increased catalytic activity in the Fenton‐like reaction and glutathione depletion capacity, further enhanced by increased temperature and LSPR. Consequently, Cu/PMCS induced better synergistic anti‐melanoma effects via PTT‐CDT than PMCS in vitro and in vivo. Furthermore, compared with PMCS, Cu/PMCS killed bacteria more quickly and effectively, thus facilitating wound healing owing to the enhanced photothermal effect and slow release of Cu2+. Cu/PMCS promoted cell migration and angiogenesis and upregulated the expression of related genes to accelerate wound healing. Cu/PMCS has potential applications in treating melanoma and repairing wounds with its antitumor, antibacterial, and wound‐healing properties.