The internal microstructure of a tablet, such as pore geometry and pore volume, impacts the tablet’s disintegration kinetics. Ideally, one could design the microstructure to control dissolution onset and therapeutical performance of immediate-release formulas; however, manufacturing tablets with a desired microstructure can be challenging due to the interplay between formulation and process parameters. Direct quantification of tablet microstructure can provide a framework for optimizing composition and process parameters based on a Quality-by-Design approach. This article reviews the importance of tablet microstructure design and liquid transport kinetics to help optimize the release and dissolution profiles of immediate-release products. Additionally, the formulation and process parameters influencing the tablet microstructure and liquid transport kinetics are discussed.