Cement is the most widely used binding material in the construction industry but also releases carbon dioxide emissions during its production. To reduce carbon dioxide emissions, several alternative cementitious materials have been tried to minimize cement content, owing to pozzolanic characteristics of the alternatives offering suitable partial replacements to cement. One such pozzolanic material is waste glass powder (GP), around the world; tons of waste glass are produced and dumped in landfills, which contaminates the soil. Waste glass has presence of high silica in the form of oxide which can help in the pozzolanic reactions in the mortar. Nanomaterials have shown positive results in concrete, due to their characteristics, they have significant effects in reducing overall porosity, which ultimately enhances durability of the concrete. In this study, nano-titanium dioxide (TiO2) is used as an addition along with waste GP as a partial replacement to cement. Cement is replaced with waste GP ranging from 5% to 20% with an increment level of 5%, nano-TiO2 is added to binder at 0.5%, 1%, and 1.5%. Setting time of the mixes is evaluated due to presence of waste glass powder and nano-TiO2 along with compressive strength. It is noted that addition of nano-TiO2 decreases initial and final setting time of the mixes; as the replacement level of waste GP increases, there is decrease in compressive strength but because addition of nano-TiO2 decrease is arrested, mix with 10% waste GP gives maximum compressive strength. Scanning electron microscope is used to study microstructure; it suggests dense microstructure with the inclusion of waste GP and nano-TiO2. The optimal combination of waste GP and nano-TiO2-induced cement mortar is achieved by optimizing the mixes using response surface methodology.