<p>Heterocyclic compounds hold significant importance in medical chemistry. Pyrimidinone is a prominent heterocycle in this domain, demonstrating diverse medical applications including anticancer, antibacterial, antidiabetic, and anti-inflammatory properties. This review highlights current advancements in the synthesis of pyrimidinone derivatives by both traditional and environmentally friendly methods, and illustrates several chemical reactions associated with pyrimidinones. Additionally, the discussion encompasses the broad-spectrum therapeutic potential and industrial significance of pyrimidinone scaffolds. Ultimately, this research highlights that the advancement of pyrimidinone synthesis from 2022 to 2025 signifies not merely a technical transition but a strategic move towards high-efficiency, sustainable drug development that connects laboratory innovation with clinical applicability.</p> Graphical abstract <p></p>