Metal–organic framework (MOF) nanozymes have garnered widespread attention in the field of biomimetic catalysis due to their highly controllable porous structure and surface functionalization, enabling them to mimic the catalytic activity and specificity of natural enzymes while offering greater stability and reusability. In recent years, significant progress has been made in the theoretical computation studies of MOF nanozymes' catalytic reactions, providing deep insights into their catalytic and analytical mechanisms. This review comprehensively gathers the latest research progress of theoretical calculation–driven MOF nanozymes on their catalytic mechanisms and applications. First, the methods that can be used for theoretical calculations of MOF nanozymes, especially density functional theory (DFT), are reviewed to help deeply analyze the active site distribution, electron transfer pathways, and adsorption and activation mechanisms of reactants of MOF nanozymes. Subsequently, this review deeply studies the contribution of these theoretical calculation methods to revealing the catalytic reaction mechanism of MOF nanozymes (such as active sites and enzyme‐like activity), especially the specific role of electron transfer and reaction energy changes in key reaction steps. Finally, this review looks forward to the challenges and opportunities in the theoretical computation for the future design and application of MOF nanozymes, especially in accurately predicting catalytic activities, understanding complex reaction mechanisms, and guiding the synthesis of new nanozyme materials. By integrating theoretical calculations with experimental research, the study of MOF nanozymes is expected to forge new avenues in biomimetic catalysis and provide effective strategies for addressing challenges in the fields of sensing, biomedicine, and environmental protection.
