Building energy demand impacts a myriad of interconnected economic, societal, and environmental aspects. As a result, Buildings Energy Models (BEM) play an important role in the process of urban design and planning. While previous studies have investigated the effects of building interventions on energy efficiency, their applicability may be limited due to the BEM’s high computational complexity. This limits their ability to systematically study important aspects of energy demand on a large scale. The development of Machine Learning Models (MLM) allows to design the required detailed analysis and solutions, while reducing the computational burden, making MLM attractive for urban designers. The capability of MLM to generalize well for multiple contexts (in our case, multiple buildings) is a crucial contributor to their applicability. However, the validation process in a wider context is often overlooked, therefore its generalization capabilities are not quantified. In this paper, we present a framework to train and validate a surrogate model derived from a physics-based BEM. Our method employs a Multiple Linear Regression model to predict Energy Use Intensity (EUI) for office buildings in Singapore using 36 input parameters (covariates), based on a training dataset of 23,000 samples. Model validation is performed by comparing the results of the Surrogate Model (SM) to a widely used BEM for a sample of 120 buildings. Our results indicate that the SM has an accuracy of NRMSE of 13%, NMBE of −3.56%, and R2 of 0.92, which suggests it can effectively and accurately predict building EUI. We also conduct a sensitivity analysis, which indicates that the parameters associated with internal loads and internal space usage are the most influential. Additionally, we present a reduced order model trained with only the 11 most influential parameters, which exhibits negligible loss in accuracy compared to the full SM while providing reduced complexity. Finally, we demonstrate an application of our SM to evaluate energy efficiency under uncertainty scenarios. The analytically derived results indicate a potential reduction of EUI of offices in Singapore from 227kWh/m2 to 99kWh/m2 by altering the building parameters that were identified as most influential.