The aim of this study was to compare the influence of heat treatment on fracture resistance (FR) of different ceramic materials used for CAD/CAM systems. Methods: Eighty monolithic restorations were designed using the same parameters and milled with a CAD/CAM system (CEREC SW 5.0, PrimeMill, Dentsply-Sirona™, Bensheim, Germany), forming five study groups: Group 1 (n = 10), CEREC Tessera (Dentsply-Sirona™, Bensheim, Germany) crystallized (CCT), Group 2 (n = 10), CEREC Tessera uncrystallized (UCT), Group 3 (n = 20), Emax-CAD (Ivoclar Vivadent, Schaan, Liechtenstein) (CEC), Group 4 (n = 20), Vita Suprinity (Vita Zahnfabrik, Bad Säckingen, Germany) (CVS), and Group 5 (n = 20) Cameo (Aidite, Qinhuangdao, China) (CC). Results: The average FR was similar for CCT, CC, and CEC at above 400 N, while CVS and UCT had the lowest values at 389,677 N and 343,212 N, respectively. Conclusion: Among the three ceramic materials that exhibited an FR above 400 N, CCT was considered the first recommended choice for CAD/CAM systems. This material not only demonstrated the highest FR but also exhibited outstanding consistency in the related measurements without the presence of outliers. Although the CC material showed high FR, its high dispersion revealed inconsistencies in the repetitions, suggesting caution in its use.