The use of materials for computer-aided design/computer-aided manufacturing (CAD/CAM) has been rapidly increasing in daily practice. However, one of the main issues regarding modern CAD/CAM materials is their aging in the oral environment, which may lead to significant changes in their overall properties. The aim of this study was to compare the flexural strength, water sorption, cross-link density (softening ratio%), surface roughness, and SEM analysis of three modern CAD/CAM “multicolor” composites. Grandio (Grandio disc multicolor—VOCO GmbH, Cuxhaven, Germany), Shofu (Shofu Block HC—Shofu Inc., Kyoto, Japan), and Vita (Vita Enamic multiColor—Vita Zahnfabrik, Bad Sackingen, Germany) were tested in this study. They were prepared in stick-shaped specimens and submitted to different tests after several aging protocols, such as thermocycling and mechanical cycle loading challenge. Further disc-shaped specimens were also created and tested for water sorption, cross-link density, surface roughness, and SEM ultramorphology, before and after storage in an ethanol-based solution. For flexural strength and ultimate tensile strength, Grandio showed the greatest values both at baseline and after aging (p< 0.05). Grandio and Vita Enamic presented the highest modulus of elasticity and the lowest water sorption (p< 0.05). A significant reduction (p< 0.05) in microhardness after ethanol storage (softening ratio%) was observed especially in Shofu. Grandio had the lowest roughness parameters compared to the other tested CAD/CAM materials, while ethanol storage significantly increased the Ra and RSm values in Shofu (p< 0.05). Despite the comparable modulus of elasticity of Vita and Grandio, this latter showed greater flexural strength and ultimate tensile strength both at baseline and after aging. Hence, Grandio and Vita Enamic may be employed for the anterior teeth and for those restorations requiring load-bearing capacity. Conversely, aging seems to affect several properties of Shofu, so its use for permanent restorations should be well-pondered based on the clinical situation.