Intraoral thermal variations may adversely affect the flexural properties of novel biomaterials for intelligent CAD/CAM fabrication of fixed partial dentures (FPDs). This study aimed to evaluate the flexural strength, flexural modulus, and effect of thermal aging on CAD/CAM restorative materials. Five CAD/CAM materials were investigated: nano-ceramic-hybrid (GR), polymer-infiltrated-ceramic-network (VE), polyether-ether-ketone (PK), fiberglass-reinforced epoxy-resin (CT), and Feldspar Ceramic (VB). A total of 100 bar-shaped specimens were prepared (N=20). Each group was subdivided into thermocycled and non-thermocycled subgroups (n=10). All the specimens underwent a 3-point bending test. The mean flexural strengths and moduli were statistically analyzed using paired t-test, analysis of variance (ANOVA), and Bonferroni pair-wise comparison (p<0.05). Significant differences were observed in the flexural strength and modulus between the materials(p<0.001). Non-thermocycled CT had the highest flexural strength (924.88±120.1MPa), followed by GR (385.13±90.73MPa) PK (309.56±46.84MPa). The flexural strength of VB was the lowest (p<0.001), but similar to that of VE. Only VE significantly decreased in flexural strength after thermocycling (p=0.002). It can be concluded that nano-ceramic-hybrid materials had higher flexural strength than feldspar ceramic and other resin/polymeric CAD/CAM materials. The materials were more resistant to thermocycleling. Their flexural strength was comparable to polyether-ether-ketone for CAD/CAM frameworks, which is suitable for higher stress loads.