The aim of our present research is to investigate possible solutions for the achievement of indoor comfort with the absence of any draft risks in the occupied zones of Cultural Heritage school building. A simple method for sustainable, reversible, and easily maintainable operations on the plant system, oriented to indoor comfort improvement and possible building-plant system refurbishment, is provided. It is based on thermal comfort assessment at an early design stage, carried out by dynamic simulation and CFD techniques. It helps to identify major ineffective equipment in historical school buildings, and potential sustainable, noninvasive, reversible, and conservative measures. Results obtained by a simulation exercise of a historical school building, a check case study, showed that the evaluation of thermal comfort conditions can be a strong guideline for reversible plant design. This guarantees building protection and preventive conservation. Refurbishment and retrofitting solutions, with a lower impact can be identified. Thus in depth assessment of the building physics and plant performance aiming at energy efficacy and sustainability, can contribute to finding out the balance between energy saving, sustainability, and quality of life. Our method can be a useful tool for effectiveness analysis on retrofit and refurbishment measures for similar case studies.