When acquired or congenital defects need restoration, maxillofacial silicone is the material of choice. Silicone, nevertheless, is far from perfect in quality. The primary objective of this research was to examine the effect of adding yttria-stabilized zirconia nanoparticles (YSZNPs) (0.5 and 1% by weight) on the wettability, surface roughness, atomic force microscopy (AFM), and X-ray diffractometer (XRD) properties of maxillofacial silicone (VST-50) room temperature vulcanization (RTV). The data were analyzed statistically. The YSZNPs were introduced to the VST-50 RTV in percentages of 0.5% and 1% by weight. A total of 63 samples of VST-50 RTV maxillofacial silicone were prepared and tested. Each group was subdivided into three identical subgroups. For the wettability test, the mean value of the 1 wt% YSZ experimental group showed the lowest wettability, followed by the 0 wt% YSZ experimental group. The 0.5 wt.% YSZ showed the highest wettability. The mean value of surface roughness decreased as the percentage of YSZNPs increased. The results of the XRD analysis performed on the YSZ nanopowder revealed the presence of multiple peaks and the crystalline structure of nanoYSZ. Furthermore, studying AFM revealed that, as the percentage of nanoparticles increased, the surface roughness decreased. Conclusion: The addition of 0.5% YSZNPs to VST-50 RTV maxillofacial silicone enhanced wettability and a non-significant decrease in surface roughness.