Computer-aided design/computer-aided manufacturing (CAD/CAM) technology has revolutionized restorative dentistry by enabling the creation of precise dental prosthetics from biocompatible materials. This integration allows for the design of complex 3D models and restorations using CAD software, which are then transferred to the CAM software to fabricate the restorations using milling machines. Critical milling settings like spindle speed, feed rate, and coolant selection are crucial for achieving optimal results based on the chosen biocompatible material. These materials, including glass ceramics, composite resins, hybrid ceramics, and zirconia, each play a specific role based on their properties. This synergy between CAD/CAM and biocompatible materials has led to significant advancements in dental restorations, improving accuracy, efficiency, and the ability to customize treatment for individual patients. The current review explores the synergistic relationship between the material science, manufacturing settings within the domain of CAD/CAM technology. Besides, it provides a comprehensive examination of various materials commonly employed in CAD/CAM, highlighting their advantages, disadvantages, and specific applications.