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Due to the low mechanical performances of 3D-printed denture base resins, ZrO₂ nanoparticles (ZrO₂NPs) were incorporated into different 3D-printed resins and their effects on the flexure strength, elastic modulus, impact strength, hardness, and surface roughness were evaluated. A total of 286 specimens were fabricated in dimensions per respective test and divided according to materials into three groups: heat-polymerized as a control group and two 3D-printed resins (NextDent and ASIGA) which were modified with 0.5 wt.%, 1 wt.%, 3 wt.%, and 5 wt.% ZrO₂NPs. The flexure strength and elastic modulus, impact strength, hardness, and surface roughness (µm) were measured using the three-point bending test, Charpy’s impact test, Vickers hardness test, and a profilometer, respectively. The data were analyzed by ANOVA and Tukey’s post hoc test (α = 0.05). The results showed that, in comparison to heat-polymerized resin, the unmodified 3D-printed resins showed a significant decrease in all tested properties (<i>p</i> < 0.001) except surface roughness (<i>p</i> = 0.11). In between 3D-printed resins, the addition of ZrO₂NPs to 3D-printed resins showed a significant increase in flexure strength, impact strength, and hardness (<i>p</i> < 0.05) while showing no significant differences in surface roughness and elastic modulus (<i>p</i> > 0.05). Our study demonstrated that the unmodified 3D-printed resins showed inferior mechanical behavior when compared with heat-polymerized acrylic resin while the addition of ZrO₂NPs improved the properties of 3D-printed resins. Therefore, the introduced 3D-printable nanocomposite denture-base resins are suitable for clinical use.