The establishment of an in vitro–in vivo correlation (IVIVC) is considered the gold standard to establish in vivo relevance of a dissolution method and to utilize dissolution data in the context of regulatory bioequivalence questions, including the development of dissolution specifications. However, several recent publications, including industry surveys and reviews from regulatory agencies, have indicated a low success rate for IVIVCs, especially for immediate-release formulations. In recent years, the use of physiologically based pharmacokinetics (PBPK) and absorption modeling, as a tool to facilitate formulation development, has been attracting increased attention. This manuscript provides an industry perspective on the current challenges with establishing IVIVCs and the potential PBPK and absorption modeling offer to increase their impact. Case studies across both immediate-release and extended-release formulations from five pharmaceutical companies are utilized to demonstrate how physiologically based IVIVC (PB-IVIVC) may facilitate drug product understanding and to inform bioequivalence assessment and clinically relevant specifications. Finally, PB-IVIVC best practices and a strategy for model development and application are proposed.