The Egyptian cultural heritage thrives in historical buildings, yet the recent urbanization has led to densely packed cities with overshadowing and poor ventilation, compromising indoor environmental quality, especially for heritage preservation. While regulations exist, interventions are needed to enhance thermal performance without harming integrity. This research seeks to parametrically investigate the thermal performance of a residential multi-story heritage building, evaluating the appropriate interventions that uphold their preservation in Cairo’s hot-desert climate. The methodological procedure is realized through two phases. This first entails an inclusive review of existing literature, examining influential factors, intervention methods, and utilized materials in heritage buildings to mitigate energy use. The annual simulations of energy consumption are carried out in the second phase, where the quantitative performances of 56 different cases are predicted, related to the application of insulation glazing systems. The results revealed a notable decrease in energy consumption, compared to the existing case, by 70–80% across the investigated systems, which include aerogel, polystyrene, air and fiber. This work aims at providing architects with realistic intervention approaches for heritage buildings, recovering the lost indoor quality of users in such contexts.