Analyzing the Köppen–Geiger climate classification and available climate data for the southern European Mediterranean coast, eight reference geolocations were selected for this analysis: the cities of Valencia, Barcelona, Marseille, Rome, Koper, Split, Athens and Nicosia. The first part of the research applies the climate potential for natural ventilation (CPNV) methodology that evaluates the theoretical availability of natural ventilation (NV) for each city location corresponding to human hygrothermal conditions. The second part of the article evaluates possible cooling energy savings (ES) applying the advanced natural ventilation (ANV) space-cooling strategy. A hypothetical four-story atrium office building model is designed for the building performance simulation (BPS) using mixed-mode (or hybrid-mode) and night-time natural ventilation (NNV) approaches. The objective is to present a comparison overview of possible space cooling ES between chosen geolocations. In the context of the current European Union’s (EU) energy transition (ET) process, the article displays ANV possibilities, as a renewable energy source (RES), in the reduction of building space cooling energy demands (ED) on the electricity grid.