Using nanomaterials to replace part of cement is one of the effective ways to enhance the performance of cement-based materials. In this study, the response surface analysis method was used to design an experiment. Through tests on the mechanical properties, the coefficient of water saturation, the shrinkage properties, and the high-temperature calcination of cement-based materials, the effects of three factors, namely, the substitution amount of nano-zinc oxide for cement, the substitution amount of nano-zirconia for cement, and the water-cement ratio, on cement-based materials under different conditions were compared and analyzed. The lower limit of the compressive strength of the cement-based materials increased by 88.17%, and the upper limit increased by 15.14% by using nano-zinc oxide and nano-zirconia to replace part of the cement. The compressive strength of cement-based materials with a nano-zinc oxide content in the range of 0.4-0.6% was low because of the low content of CSH. The coefficient of water saturation decreased with an increase in age, and the coefficient of water saturation of high-performance concrete was low. Nano-zirconia had a significant effect on the mass loss of autogenous shrinkage and the mass loss of drying shrinkage. When the substitution amount of nano-zinc oxide was 0.4-0.8%, the mass loss was large. In summary, with its unique microscopic characteristics, nanomaterials could significantly improve the performance of cement-based materials with regards to their mechanical properties, durability, workability, and other aspects.