Climate change has severely threatened human settlements and building efficiency in recent years. Implementing systems with low energy consumption without affecting thermal comfort is essential. This chapter presents an overview of successful past bioclimatic studies to the present, a bioclimatic diagnostic of 16 cities in Southern Mexico, and shows the results of applying thermal inertia strategies in a case study for one of the cities bioclimatically diagnosed. Data monitoring and collection determined the bioclimatic zones and thermal comfort indices. The analysis results indicated that most cities (82.2%) do not have an acceptable thermal comfort level. However, the applied methodology allowed the identification of bioclimatic strategies and heating-cooling requirements of the cities studied. The case study of Valles Centrales in Oaxaca showed how the passive design strategy helped to get thermal comfort in a real-scale prototype house successfully using a hybrid system based on prefabricated reinforced mortar channels filled with soil-cement-sawdust as a thermal inertia passive strategy. In this way, CO2 emissions are reduced from air-conditioning in living spaces, positively impacting climate change whenever adequate passive strategies are implemented successfully.