Rational and Multidimensional Optimization of Nanozyme Catalytic Performance

ABSTRACT Nanozymes are a class of nanomaterials with intrinsic biocatalytic activities. Compared to natural enzymes, they offer superior stability, precise structural tunability, and significant cost‐effectiveness. Beyond serving as robust alternatives, nanozymes play increasingly pivotal roles in environmental monitoring, biosensing, and biomedical diagnostics. Despite significant strides, the rational orchestration of nanozyme activity remains elusive, primarily due to the intricate synergistic effects between atomic coordination environments, modulated electronic states, and interfacial microenvironments. In this review, we present a comprehensive and rational perspective on the multidimensional optimization of nanozyme catalytic performance. We first summarize the fundamental catalytic mechanisms and representative classes, emphasizing structure‒activity relationships at the nanoscale. Subsequently, strategies for enhancing performance are systematically discussed from two dimensions: intrinsic material regulation, including oxidation‐state modulation and defect engineering, and extrinsic environmental regulation, such as pH and temperature. Furthermore, recent advances in theoretical calculations and machine learning‐assisted approaches are critically reviewed, highlighting their emerging roles in guiding mechanism‐informed and data‐driven nanozyme design. By integrating mechanistic insights with intrinsic and extrinsic regulation strategies, this review aims to establish a unified framework for the rational optimization of nanozyme performance and provide guidance for future development.