Optimizing the performance of drug products requires a strong understanding of the interplay between material properties, manufacturing process parameters, and tablet performance. Microstructure is a crucial intrinsic property that details the spatial and material arrangement that can be examined in a rapid nondestructive scan. Here, we aim to demonstrate the development of a nondestructive, image-based microstructural characterization with potential to rapidly troubleshoot tablet performance with custom analysis. X-ray computed microtomography (micro-CT) is used alongside 3D advanced imaging techniques to examine the spatial distribution of tablet coating and porosity to then model the effect of porosity under simulated dissolution. The benefits of a developed microstructural analysis cannot be overstated, as it has the potential to routinely provide a mechanistic basis to understand, predict, and troubleshoot tablet performance.