Introduction: This study aims to determine and compare the fracture strength and failure modes of zirconia-reinforced lithium silicate glass ceramics (ZLS) and yttria-stabilized zirconia-based ceramic MOD and MO inlay restorations. Materials and Methods: Stumps representing the maxillary second premolar were prepared using HyperDent software and CAD/CAM milling units. Thirty-two epoxy resin die models were obtained, with 16 samples in each group. Subsequently, restorations were fabricated using Vita Suprinity (VITA Zahnfabrik, Bad Sackingen, Germany) and IPS e.max ZirCAD CAD/CAM (Ivoclar et all., Liechtenstein) blocks to restore the inlay cavities. The specimens were subjected to aging and then tested for fracture using a universal testing machine. The resulting fractures were classified. Data normality was assessed using the Shapiro-Wilk test, and homogeneity of variances was evaluated using the Levene test. The interaction between restorative material type and cavity surface was tested using two-way ANOVA. Results: The fracture strength of IPS e.max ZirCAD material (mean value: 723.18±57.51) is higher than that of Vita Suprinity ZLS material (689.86±113.61), but this difference is not statistically significant (F=3.46, p=0.073). The group with 3-surface cavities in the tooth material (768.00±60.60) has significantly different fracture strength compared to the group with 2-surface cavities (645.037±71.20) (F=47.18, p<0.001). Conclusions: Having a 3-surface cavity may further enhance the fracture resistance of inlay restorations, and this difference is statistically significant. There is no significant difference in fracture strength among restorative materials.