Building insulation based on nanomaterials is considered one of the most effective means of reducing energy consumption in the hot desert climate. The application of an energy-efficient insulation system can significantly decrease the energy consumed via a building’s air-conditioning system during the summer. Hence, building insulation has become an interesting research topic, especially with regards to the use of insulation based on nanomaterials due to their low U-values. In the present study, the use of nano vacuum insulation panels (VIPs) or polystyrene foam in the walls enabled a significant reduction in the annual energy consumption, a savings of 23% compared to the uninsulated wall in a study in New Aswan City. The application of nanogel glazing to the windows (two layers of clear glass filled with the nanogel) achieved approximately 11% savings in annual energy. This savings, twice that obtained by using double-glazed windows, could be due to the low U-value of nanogel compared to the U-values of argon or air. The embedded nanogel layer between two layers of argon and two layers of single clear glass showed a significant reduction in annual energy consumption, saving 26% compared to the use of a single layer of glass. Moreover, the integration between this window and embedded walls with 50 mm of polystyrene foam exhibited a significant improvement of energy efficiency by 47.6% while presenting the lowest value of simple payback period (SPP). This research provides a way for buildings to be insulated to make them more energy efficient as well as attractive from the economic standpoint.