Utilities are increasingly interested in integrating energy efficiency and demand response measures as a strategic approach that aims to achieve an increasingly reliable, dynamic, and integrated electric system. The concepts of energy efficiency (EE), demand response (DR), and system reliability (ESR) have been mainly studied from a different perspective, dealing only with the interaction between EE and DR and between EE and ESR. This paper aims to improve knowledge and demonstrate the validity of EE interventions (EEIs) through the use of a tool for evaluating the benefits of energy efficiency measures (EEMs) in the environmental sphere and in terms of DR and ESR. In order to evaluate this interaction, a quantitative method is proposed and validated on real results in an Italian case scenario, taking into account the analysis of smart meters data for residential users located in southern Italy in Calabria. Based on the collected data, an aggregation of users was evaluated with real hourly profiles covering the period from January 2020 to August 2020. These results show how efficient energy use may affect DR resource availability and power systems reliability. In conclusion, the authors justify that a more reliable electric system is ready for new types of EE financing systems based on pay-for-performance contracts.