<p>Roll compaction/dry granulation and tableting (RCDG-T) process frequently impacts the quality and efficiency of tablets due to the loss of tabletability (LoT). The process parameters have a major impact on this issue, which arises from the multi-scale interaction between the raw material powder, the ribbon, and the particle properties. The cross-scale transmission of material properties and the dynamic coupling of process parameters are difficult to uncover through traditional research, and the fundamental mechanism of LoT remains unclear. It is necessary to build a methodical technique that integrates multi-scale material evolution with process parameters in order to investigate the compaction mechanism of this process. The structural reorganization of granular systems under processing circumstances, starting with micro-scale bonding, moving through mesoscale force chains and pore network evolution, and finally dictating macroscopic features, is the fundamental process of tablet manufacturing. Therefore, it is crucial to establish systematic characterization methods that encompass micro-, meso-, and macro-scales to gain a deeper understanding of this process and optimize tablet quality. This review aims to establish a multi-scale research framework for the RCDG-T process, with an emphasis on the interactions between material attributes and process parameters at each scale. This work will elucidate cross-scale causal relationships from process conditions to macroscopic properties, review characterization and monitoring techniques for key material properties and process parameters, and explore the role of computational simulation in mechanism analysis and performance prediction, along with the feasibility of constructing predictive digital twins. Integrating these multi-scale insights will establish a scientific foundation for developing mechanism-based process digital twins.</p>