Purpose: To evaluate the fracture load of monolithic zirconia crowns with implant screw holes, focusing on variations in occlusal and axial thicknesses, and to assess the interaction between these variables. Materials and Methods: Six different prostheses were designed using CAD software, varying in occlusal thickness (0.5 mm, 1.0 mm) and axial thickness (0.4 mm, 0.8 mm, 1.2 mm) based on the height and thickness differences of the titanium implant abutment. Twelve specimens per design were created by milling zirconia blocks and titanium abutments. These specimens were cemented with resin and subjected to thermomechanical aging (50 N, 200,000 cycles, 5°C-55°C, 30 seconds dwell time) using a chewing simulator. Static loading was applied using a universal testing machine at a rate of 0.5 mm/min until fracture occurred, and the load value (N) at the moment of the initial fracture was recorded. Fracture pattern and surface analyses were performed. Statistical analyses included two-way analysis of variance, Tukey HSD test, multiple regression analysis, and Fisher’s exact test. Results: Both occlusal and axial thicknesses significantly influenced the fracture load (P < .05), with a significant interaction between them (P < .05). An occlusal thickness of 1.0 mm exhibited a significantly higher fracture load compared to 0.5 mm (P < .05). An axial thickness of 1.2 mm showed a significantly higher fracture load compared to 0.4 mm and 0.8 mm (P < .05). The difference in axial thickness between 0.8 mm and 1.2 mm had a more substantial impact on fracture load than the difference in occlusal thickness between 0.5 mm and 1.0 mm (P < .05). Fractographic analysis showed that the thin axial wall exhibited twist hackles without involvement of the crown margin, whereas the thick axial wall exhibited no hackles and a more catastrophic failure involving the crown margin. Conclusion: For monolithic zirconia crowns with implant screw holes, when sufficient occlusal thickness cannot be achieved, an axial thickness of at least 1.2 mm is recommended to ensure higher fracture resistance.