Understanding the factors driving the implementation of energy efficiency measures in compressed air systems is crucial to improve industrial energy efficiency, given their low implementation rate. Starting from a thorough review of the literature, it is thus clear the need to support companies in the decision-making process by offering an innovative framework encompassing the most relevant factors to be considered when adopting energy efficiency measures in compressed air systems, inclusive of the impacts on the production resources and the operations of a company. The framework, designed following the perspective of the industrial decision-makers, has been validated, both theoretically and empirically, and preliminarily applied to a heterogeneous cluster of manufacturing industries. Results show that, beside operational, energetic, and economic factors, in particular contextual factors such as complexity, compatibility, and observability may highlight critical features of energy efficiency measures whose absence may change the outcome of a decision-making process. Further, greater awareness and knowledge over the important factors given by the implementation of the framework could play an important role in fostering the implementation of energy efficiency measures in compressed air systems. The paper concludes with further research avenues to further promote energy efficiency and sustainability oriented practices in the industrial sector.