Thermal comfort plays a crucial role in shaping the indoor environment of school buildings, with direct implications for student well-being and academic achievement. This study enhances the dynamic energy analysis of school buildings by investigating the intersection between objective thermal comfort assessments and occupants’ needs. Focusing on a school in Central Italy, the research highlights how energy-inefficient infrastructure can impact occupant comfort and thinking performance outcomes. The study offers a general understanding of how environmental factors can influence students’ well-being and cognitive function by establishing a quantifiable relationship between Predicted Mean Vote (PMV) values and productivity loss in thinking tasks. The research employs a range of climatic datasets, including historical, current, and projected future data, to analyse the building’s performance across varying climate conditions. The results reveal significant thermal discomfort in the older section, particularly during peak temperature periods, while the newer building section demonstrates superior thermal performance. Notably, implemented energy retrofit measures successfully reduced summer discomfort projections by up to 66% through 2070, simultaneously decreasing cognitive impairment by up to 63%. Beyond technical considerations of energy efficiency, climate change mitigation, and cost savings, this research advocates for a paradigm shift in architectural and policy approaches, placing human-centric design at the forefront. It emphasizes the imperative for architects, engineers, and policymakers to integrate thermal comfort and cognitive performance alongside sustainability goals in the planning and renovation of educational spaces. By promoting a balanced approach, the study underscores the necessity of designing learning environments that support both well-being and academic success.