Most energy exchanges take place through the building skin. The skin characteristics play a decisive role in the extent of these exchanges, but they are somewhat more varied in the double skin façade (DSF). Among these characteristics, cavity segmentation has a noticeable effect on the implementation of the DSF in different directions during the hot and cold seasons. The aim of this study was to investigate the role of DSF segmentation in energy consumption and natural ventilation of high-rise buildings in hot and dry climates. This study used DesignBuilder software to study sixty-four segmentation component scenarios in an eight-story residential building in Isfahan, Iran. Moreover, a proposed hybrid model utilizing the hybridization of the Hunger Game Search and Gradient Boosting (HGS-GB) algorithm was employed to estimate energy consumption in various scenarios involving lighting, heating, cooling, and total scenarios. The available outcomes revealed that the HGS-GB model had a better performance in comparison with other individual models, such as Gradient Boosting (GB), Random Forest (RF), and K-nearest neighbors (KNN). The R2 values for lighting, heating, cooling, and total energy estimation were 0.9993, 0.9958, 0.9991, and 0.9922, respectively. The findings of this study suggest the significance of DSF segmentation in energy consumption and natural ventilation in high-rise buildings in hot and dry climates.