This study examines the challenges faced by educational institutions in the Mediterranean region in managing energy costs and thermal comfort, with a particular focus on the impact of climate change. Global temperatures are expected to increase by about 1–1.5 °C by 2040 and 1.5–3.5 °C by 2080, which could worsen environmental conditions in schools. The research examines the variation in comfort levels in schools, considering different future perspectives over a long period of time. Specifically, it focuses on the predicted thermal performance of a classroom in Lecce, a city in southern Italy. Long-term hourly dynamic thermal simulations have been performed for the year 2050. The study is structured in three, namely the analysis of the evolution of the indoor operative temperature, the effectiveness of ventilation in ensuring thermal comfort in winter, and the evaluation of indoor temperatures between current and future long-term climatic data. Ten ventilation scenarios were used for air exchange, with the aim of maintaining an operative indoor temperature between 21 °C and 23 °C during the winter period. The results highlight the critical challenge that climate change poses for schools and underline the importance of adopting integrated approaches that take into account energy efficiency, environmental impact, and the well-being of students and staff. In Mediterranean regions, one possible solution could be to discourage the installation of heating systems and promote the adoption of controlled mechanical ventilation systems.