Directive 2024/1275/EU established that Member States should set requirements for the implementation of adequate indoor environmental quality standards to maintain healthy indoor climate. Specifically, buildings need to be designed and managed to meet people’s requirements and provide a safe, healthy and productive indoor environment. Air handling unit (AHU) is a key technology to respond to these challenges. A major problem related to traditional AHU is the air leakages, which can lead to reduced operating efficiency and increased consumptions. For this reason, the paper aims to show the multiple benefits of an innovative high air-tight treatment unit, able to guarantee the maximum air leakage tightness and prevent humidity infiltration, compared to a reference AHU. Moreover, its combination with innovative auxiliary equipment (e.g., biocidal or photocatalytic air filters) able to limit the spread of contaminants, bacteria and viruses, makes this innovative solution in line with the main EPBD requirements related to indoor environmental quality. The study consists of two main objectives: (i) the assessment of potential energy savings resulting from the installation of the innovative AHU, considered as a box with high air tightness; (ii) the evaluation of the investment payback period of the innovative AHU installed in a reference building. Results demonstrate the goodness and readiness of the new high air-tight handling unit to be introduced on the market, proving both energy-efficient and cost-effective. Specifically, results show 11–14% energy savings due to reduced air leakage. Despite a 3% higher investment, savings enable a one-year payback, enhancing occupants’ well-being and sustainability.