Metal ion‐enzyme tandem systems hold immense potential for biocatalysis, environmental remediation, and medical therapy, yet their development is hindered by inherent incompatibility, low ion concentration, and spatial distance barriers between metal ions and enzyme, limiting the maximization of metal ion catalytic potential. Here, we developed a convenient one‐step doping strategy to achieve spatial separation of high concentration metal ions and enzymes within single metal‐organic frameworks (MOFs). Catalytically active metal ions partially replace MOF sites through ligand coordination, while enzymes are in‐situ encapsulated (enzyme@M‐MOFs), maintaining structural integrity and enhancing stability. This design enables efficient chem‐bio tandem reactions by preventing mutual inactivation and accelerating reaction rates due to distance shortening between metal ions and enzymes. The enzyme@M‐MOFs exhibit good therapeutic effect in diabetic wound healing, establishing a new paradigm for catalytic medicine applications. The strategy's versatility is demonstrated by its successful application with a range of metal ions (Fe²⁺, Mg²⁺, Cd²⁺ …) as catalysts or enzyme promoters. By transforming incompatible systems into compatible tandem platforms, this work offers a universal approach for efficient chemical‐enzyme tandem catalysis, unlocking novel possibilities in biocatalysis and beyond.

Metal-organic framework (MOF) nanosheets and covalent organic framework (COF) nanosheets as emerging porous materials nanosheets have captured increasing attention owing to their attractive properties originating from the advantages of large lateral size, ultrathin thickness, tailorable physiochemical environment, flexibility and highly accessible active sites on surface, and the applications of them have been explored in a wide range of fields. Although MOF and COF nanosheets own many similar properties, their applications in various fields show significant differences, probably due to their different compositions and bonding modes. Hence, we summarize the recent progress of MOF and COF nanosheets by comparative analysis on their advantages and limitations in synthesis and applications, providing a more profound and full-scale perspective for researchers or beginners to understand this field. Herein, the categories of preparation methods of MOF and COF nanosheets are firstly discussed, including top-down and bottom-up methods. Secondly, the applications of MOF and COF nanosheets for separation, catalysis, sensing and energy storage are summarized. Finally, based on current achievements, we put forward our personal insights into the challenges and outlooks on the synthesis, characterizations, and promising applications for future research of MOF and COF nanosheets.