Background: Nowadays, the esthetics demand is continuously increasing; therefore, metal-free materials are widely used, like a zirconia-based ceramic, which is conveniently fabricated via computer-aided design and computer-aided manufacturing (CAD/CAM) system for restorations from single to full mouth rehabilitation. Objective: This study evaluated the effect of pre-curing pressure on the shear bond strength of zirconia to the resin cement. Methods: A total of sixty-three sandblasted cylindrical zirconia mounted in autopolymerizing resin were randomly assigned to three groups; Group 1: no treatment (control), Group 2: negative pressure, and Group 3: positive pressure to resin cement after resin cement application and resin composite columns bonded to zirconia. Thirty-three of the samples were stored in distilled water at 37 °C for 24 hr before the shear bond strength test for thirty samples and three samples were cross-sectionally cut for interfacial observation with FESEM. Another thirty samples were thermocycled for 5,000 cycles in distilled water at 5°C to 55 °C before testing. The shear bond strength and failure mode were evaluated. Examination of the bonding interface was also done. Results: The results were analyzed using two-way ANOVA. The means of shear bond strength of non-thermocycle of the control group were 8.01 ±1.74 MPa, 9.10 ±1.90 MPa, and 9.14 ±2.58 MPa, whereas that of thermocycle group were 5.71 ±0.84 MPa, 5.53 ±0.68 MPa, and 5.68 ±0.77 MPa in zero pressure group, negative pressure group, and positive pressure group, respectively. It showed no statistically significant differences in shear bond strength in all pressure groups (p > 0.05). The pre-curing pressure did not influence the shear bond strength of the zirconia and resin cement. Conclusion: There was no difference in the shear bond strength between the pressure groups and the no treatment control group. The positive and negative pressure did not influence the shear bond strength of the zirconia and resin cement.