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This study investigated the fracture resistance and failure modes of custom-fabricated post- and core dental restorations using various CAD/CAM materials. Seventy-five mandibular second premolars were allocated to five groups (n = 15) and prepared for standardized post and core restorations. The groups included a control group comprising cast metal and four CAD/CAM materials: Vita Enamic, Shofu HC, Trilor, and PEKK. Fracture resistance was assessed using a compressive force at a crosshead speed of 1 mm/min until failure occurred. Data were analyzed using one-way analysis of variance (ANOVA) and chi-square tests. The metal group had the highest fracture resistance (244.41 ± 75.20 N), with a significant variance compared to that in the CAD/CAM groups (p < 0.001). No significant differences were observed among the non-metallic groups. While several CAD/CAM materials displayed satisfactory flexural properties, cast metal posts showed superior fracture resistance in endodontically treated teeth but were mostly associated with catastrophic failure. The clinical application of CAD/CAM materials for post-core restorations presents a viable alternative to traditional metal posts, potentially reducing the risk of unfavorable fractures. [ABSTRACT FROM AUTHOR]