This paper discusses the effect of various climatic conditions that pertain to passive design measurements and their relationships with building configurations to improve indoor thermal comfort based on the different climate zones in Egypt to support Egypt’s sustainability agenda 2030. We find the most appropriate design settings that can increase the indoor thermal comfort, such as building orientation and shape. These settings can be modeled using DesignBuilder software combined with Egyptian meteorological data. This software is used accompanied by computational fluid dynamics to numerically assess the outcomes of different changes, by simulating indoor climate condition factors such as wind speed and temperature. Natural ventilation simulations were performed for four different shapes to create comprehensive dataset scenarios covering a general range of shapes and orientations. Seven scenarios were optimized to put forward a series of building bioclimatic design approaches for the different characteristic regions. The results indicated that the temperature decreased by about 3.2%, and the air velocity increased within the study domain by 200% in the best and the worst cases, respectively, of the four different shapes. The results of the study gave evidence that the configuration of buildings, direction, and wind speed are very important factors for defining the natural ventilation within these domains to support the green building concept and the sustainable design for a better lifestyle