The success of educational institutions is fundamentally intertwined with the well-being and academic progress of their students. In this context, indoor air quality (IAQ) and thermal comfort play a critical role in creating conducive learning environments that support both health and academic performance. This work evaluates six ventilation systems and strategies for enhancing IAQ and thermal comfort, which prevail in educational buildings in the Spanish region of Catalonia. To do so, a multi-criteria analysis is performed based on the Analytic Hierarchy Process (AHP) method, considering economic, social, and environmental aspects. Ventilation systems are pairwise compared in terms of six criteria: initial and maintenance cost, classroom air quality, students’ thermal comfort in summer and winter, and energy consumption. Subsequently, weighted combinations of these criteria are established to rank the ventilation systems under five case scenarios. The results indicate that natural ventilation systems, particularly those with atriums and courtyards (N-AAC), offer a balanced solution, achieving satisfactory IAQ and thermal comfort while being more cost-effective and environmentally sustainable in certain contexts. The variation in the best solution across different scenarios demonstrates that the optimal choice is highly context-dependent, influenced by factors such as budget, climate, and infrastructure. This research provides a valuable foundation and methodology for decision-makers in educational institutions, supporting the selection of ventilation systems that maximize sustainability while enhancing students’ comfort and fostering learning environments.