Background <p>Therapeutic antibodies have prominently emerged in oncology and are playing increasingly pivotal roles. Recently, Project Optimus launched by the FDA recognized the importance of dose optimization for safe and effective oncological treatment and highlighted the critical role of the PK/PD modeling approach in dose-related decision-making with respect to therapeutic antibodies. Various pharmacometric modeling techniques have been developed and applied in the development and clinical application of anticancer therapeutic antibodies.</p> Area covered <p>This paper provides a concise overview of the structure and function of therapeutic antibodies and summarizes the major modes of action (MoAs) of anticancer therapeutic antibodies. It subsequently reviews current PK/PD modeling techniques from empirical to mechanistic models and introduces the implementation of PK/PD modeling approaches in dose-related decision-making across both drug development and clinical applications. Moreover, current challenges along with the opportunities arising from the integration of novel technologies with PK/PD modeling are discussed. </p> Expert opinion <p>The PK/PD analysis of therapeutic antibodies in oncology is closely related to their structures and MoAs. Furthermore, the presence of target-mediated drug disposition (TMDD) and the bidirectional interaction between PD and PK increase the complexity of the analysis. Although empirical or semi-mechanistic models remain widely used, increasing evidence has demonstrated that mechanistic models offer distinct advantages in providing deeper insight into the underlying mechanisms and facilitating translational studies, particularly for immunotherapeutic antibodies. Moreover, according to the purpose of specific research, selecting one or a combination of modeling approaches to complement or validate each other can significantly increase the reliability of conclusions.</p>