Polymeric drug delivery systems (PDDS) play a crucial role in controlled drug release, providing improved therapeutic outcomes. However, formulating PDDS and predicting their release profiles remain challenging due to their complex structures and the numerous variables that influence their behavior. Traditional mathematical and empirical prediction methods are limited in capturing these complexities. Recent studies have unveiled the potential of Machine Learning (ML) in revolutionizing drug delivery, particularly in formulating complex PDDS. This article provides an overview of the significant and fundamental principles of various ML in estimating PDDS drug release behavior. Our focus extends to the accomplishments and pivotal discoveries in current research, spanning seven distinct sustained-release drug delivery systems: matrix tablets, microspheres, implants, hydrogels, films, 3D-printed dosage forms, and other innovations. Furthermore, it addresses the challenges associated with ML-based drug release prediction and presents current solutions while delving into future perspectives. Our investigation underscores the significance of Artificial Neural Networks in ML-based PDDS release profile prediction, surpassing both traditional and alternative ML-based methods. These extensive datasets can be drawn from literature-based resources or enhanced through specific algorithms. Moreover, ensemble-based models have proven advantageous in scenarios involving intricate relationships, such as a high number of output parameters. ML-based drug release prediction notably exhibits substantial promise in 3D-printed dosage forms, presenting a frontier for personalized medicine and precise drug delivery.