Resilient polymeric materials such as silicone elastomers are currently used for maxillofacial prostheses construction but the strength of these materials and their clinical performance need to be optimized with the addition of reinforcing fillers. This study investigates the effect of zirconia nanopowder addition on tear strength, tensile strength, elongation at break, Shore A hardness, surface roughness and cytotoxicity of VST-50 maxillofacial silicone. Silicone base was mixed with different amounts (1%, 2% and 3%) of zirconia nanopowder using a vacuum mixer. Silicone without filler was used as control for comparison. Scanning Electron Microscopy and Atomic Force Microscopy were utilized to assess the efficiency of high-shear vacuum mixing as filler dispersion method and the surface topography, respectively. Both SEM and AFM images showed that the zirconia nanopowder were distributed fairly well within the polymer. Statistically, highly significant increase in tear strength, tensile strength and hardness with non-significant decrease in elongation at break and non-significant increase in surface roughness were seen with 1% and 2% groups. Whereas with 3% group, there was significant improvement in tear strength, tensile strength and hardness but there was significant undesirable decrease in elongation and increase in roughness. Cytotoxicity test revealed that the addition of zirconia nanopowder was nontoxic to Rat Embryonic Fibroblast (REF) cells and there was non-significant change in the cell viability of all study groups after 24- and 72-hours incubation periods. In conclusion, the addition of 2% by weight nano zirconia to VST-50 maxillofacial silicone could be beneficial in enhancing its performance.