Background <p>Pharmacokinetic (PK) modeling is essential for understanding drug disposition within biological systems, providing crucial insights into the process of absorption, distribution, metabolism, and excretion (ADME). With the advent of advanced drug delivery systems (DDS), the demand for sophisticated PK models has grown, as they are needed to accurately predict drug release profiles, systemic exposure, and therapeutic efficacy. These models play a pivotal role in guiding rational drug design and advancing the field of personalized medicine.</p> Area covered <p>This review explores the role of pharmacokinetics in the development and optimization of DDS, with an emphasis on basic compartmental models and physiologically-based pharmacokinetic (PBPK) models that are essential for describing drug ADME in the body. It also examines how these models are applied to characterize novel DDS, including advanced formulations such as liposomes, nanoparticles, and targeted delivery systems, aiming to improve therapeutic efficacy and patient outcomes.</p> Expert opinion <p>Although significant progress has been achieved in PK modeling for DDS, a major challenge remains: accurately capturing the complex interplay among drug release mechanisms, heterogeneous tissue distribution, and inter-individual variability. Future research should focus on developing more robust, multiscale modeling strategies that bridge in vitro findings with in vivo outcomes, while also leveraging artificial intelligence and machine learning to enhance predictive accuracy and accelerate the clinical translation of innovative DDS.</p>