Purpose: The aims of this study were to evaluate the flexural strength and adhesion of zirconia-reinforced lithium silicate glass ceramic with those of lithium disilicate after applying a combined thermo-mechanical load cycling. Materials and Methods: Zirconia-reinforced lithium silicate (vita suprinity; SV) and lithium disilicate glass ceramics (IPS e.max CAD; EM) were the materials used in this study. Specimens with the required dimensions for microtensile bond strength and flexural strength test were prepared and finished. The specimens were divided into two groups: control group that was stored in distilled water at 370C for 24 h (without thermo-mechanical load cycling) and test group (with thermo-mechanical load cycling). A total of 3,500 thermal cycles and 250,000 mechanical loading cycles were performed. Microtensile bond strength and flexural strength of each material were evaluated before and after thermo-mechanical load cycling. Moreover, additional micromorphological analysis such as those involving scanning electron microscopy and surface roughness of the etched ceramic bonded surfaces were performed for qualitative analysis. Data were analyzed using independent t-tests between the two glass ceramic groups, and paired t-test was used to detect significance within each group with and without thermo-mechanical load cycling. Results: The effect of thermo-mechanical load cycling on microtensile bond strength was statistically significant for both types of glass ceramics (EM and SV) (P<.001) and the most frequent failure type was mode I (adhesive failure between cement and ceramic type) with pronounced effect on EM (66.67%) than on SV (40%). Regarding thermo-mechanical load cycling effect on flexural strength, there was statically significant difference (P<.001) only for EM. Conclusions: SV glass ceramic showed higher bonding values than EM glass ceramic only after thermo-mechanical load cycling. However, it provides higher flexural strength values either before or after thermo-mechanical load cycling than EM glass ceramic.