Reducing energy consumption is a key policy focus for mitigating climate change. This study investigates the determinants of residential building energy efficiency, leveraging expert insights from Energy Performance Certificates (EPCs) to develop a machine learning prediction framework. Datasets from countries at distinct latitudes, the UK and Italy, are analyzed to identify potential regional variations in the factors influencing energy efficiency. Findings reveal the crucial role of factors related to heating systems and insulation materials in the determination of the building’s efficiency. Also, there is evidence of the superior ability of non-linear machine learning models to capture complex relationships between building characteristics and efficiency. A scenario analysis further demonstrates the cost-effectiveness of policies informed by machine learning recommendations.