Nanozymatic reactions that produce or consume oxygen (O2) or reactive oxygen species (ROS) consist of oxidase, peroxidase, superoxide dismutase (SOD), and catalase-type activity. Although extensive studies were conducted to overcome hypoxia through nanozymatic reactions, the construction of an ideal system is challenging, given that the reactants and products are arranged in a recurring structure for continuous consumption in a full cycle. In this study, speckled Ru–Te hollow nanorods were prepared through solvothermal galvanic replacement against Te nanorod templates with high yield and robustness. From their multicompositional characteristics, nonrecurring peroxidase-SOD-catalase-type nanozymatic properties were identified with photothermal and photodynamic feasibility over a wide range of laser irradiation wavelengths. Owing to the excellent colloidal stability and biocompatibility, the proposed Ru–Te-based nanozymatic platform was highly effective in hypoxic pancreatic cancer phototherapy in vitro and in vivo by near-infrared laser irradiation mediated photothermal and photodynamic combination treatment.