Cancer is one of the leading causes of mortality worldwide. Due to the high heterogeneity of the tumor microenvironment, conventional therapeutic approaches face formidable challenges, including suboptimal efficacy and multidrug resistance. Nanozymes, particularly transition-metal bimetallic nanozymes, have become a research hotspot in the field of antitumor nanomaterials, owing to the unique electronic structures of transition metals and synergistic catalytic mechanisms between the bimetallic components. This review systematically summarizes the types of enzyme-like activities of transition-metal bimetallic nanozymes, the construction strategies for multi-enzyme cascade reactions, and their applications in antitumor therapy. It further summarizes the current challenges of these nanozymes and provides an outlook on their future directions. This review aims to provide a theoretical foundation for promoting the clinical translation of transition-metal bimetallic nanozymes in antitumor therapy.