Objectives: The purpose of this study was to evaluate the effect of different fabrication techniques on the fracture strength of the composite resin-based inlay restorations of endodontically treated molars. Methods: Sixty mandibular molars were divided into six groups (n = 10) designated according to the treatment as: Group-1: Control group, intact teeth; Group-2: Filtek Ultimate Universal restorative with incremental technique; Group-3: Filtek Bulk Fill Posterior restorative; Group-4: Biodentine with Filtek Ultimate Universal restorative; Group 5: everX Posterior with Filtek Ultimate Universal restorative; and Group-6: Lava Ultimate CAD/CAM restorative. The standard mesio-occluso-distal cavities were prepared and the roots filled for all the teeth, except those of the control group. Following the placement of the restorations, the fracture resistance of the specimens was measured. The data were analyzed by the one-way analysis of variance and Tukey's post hoc test. Results: While Group-1 (2815.80 N) exhibited significantly higher fracture strength than the other groups (p < 0.05), Groups-2 (2062.20 N), 3 (2166.00 N), 5 (2355.60 N), and 6 (2340.70 N) exhibited statistically similar results (p > 0.05). The Biodentine group (1480.50 N) exhibited significantly lower fracture strength than the rest of the groups (p < 0.05). Conclusions: The CAD/CAM and manual build-up techniques exhibited statistically similar results with the exception of Biodentine, which exhibited a significantly lower in vitro performance compared to the other composites used in the study. The fiber-supported composite everX Posterior increased the fracture strength of the endodontically treated teeth.