Modern drug delivery increasingly relies on micro- and nano-structures to achieve specific release rate and therapeutic target. The delivery systems modulate drug release via engineering control of the API domain and pore size. Other approaches involve the use of functional coating or performance-enabling excipients. The small-scale nature of pores, drug domains, and delivery vehicles demands higher resolution technique to characterize. High-resolution image-based characterization has been broadly utilized in drug product development for fundamental understanding on the process-property-performance interplay and optimizing formulation process and design. It finds applications in various novel drug release systems such as tailoring rate-limiting film coat thickness where the pore formation is critical to control drug release and interrogating the underlying mechanism of in-situ drug nanoparticle formation from amorphous solid dispersions in dissolution media for solubility enhancement. 3D micro-imaging can qualitatively visualize micro-structures, quantify their spatial and chemical distribution, and predict release behavior. In recent years, the emerging image-based numerical simulation has received significant traction and plays an important role on predicting drug release performance. Information-rich 3D images can be converted to characteristic drug transport parameters through intelligent analysis and applied to numerical simulation models to predict release performance. This image-based simulation approach represents a potential paradigm shift in drug design and evaluation, with significantly reduced evaluation time, improved release performance, and lowered in-vitro and in-vivo experiment cost.