Layered materials have become one of the focuses in chemistry and materials science due to their unique structural characteristics and highly tunable properties. Clusters with mesoscale dynamic structures can be introduced into layered materials as structural units or guests, endowing cluster-based layered materials with enhanced or emerging new properties different from those of the individual components. This review starts with a summary of the design and assembly strategies of typical cluster-based layered materials from a multiscale perspective, and then introduces the multiscale characterization and simulation platform. Additionally, we discuss the recent progress in the catalytic and energy storage application of cluster-based layered materials and summarize the current challenges and future directions in this field.