Urban building energy modeling (UBEM) is crucial for assessing energy consumption patterns at the city-scale and for supporting data driven planning and decarbonization strategies. However, its practical deployment is often hindered by the need to balance detailed physics-based simulations with acceptable computation times when thousands of buildings are involved. This work presents a large-scale real world UBEM case study and proposes a workflow that combines EnergyPlus simulations, high-performance computing (HPC), and open urban datasets to model the energy consumption of the building stock in the Municipality of Bologna, Italy. Geometric data such as building footprints and heights were acquired from the Bologna Open Data portal and complemented by aerial light detection and ranging (LiDAR) measurements to refine elevations and roof geometries. Non-geometrical building characteristics, including wall materials, insulation levels, and window properties, were derived from local building regulations and the European TABULA project, enabling the assignment of archetypes in contexts where granular information about building materials is not available. The pipeline’s modular design allows us to analyze different combinations of retrofitting scenarios, making it possible to identify the groups of buildings that would benefit the most. A key feature of the workflow is the use of Leonardo, the supercomputer hosted and managed by Cineca, which made it possible to simulate the energy consumption of approximately 25,000 buildings in less than 30 min. In contrast to approaches that mainly reduce computation time by simplifying the physical model or aggregating representative buildings, the HPC-based workflow allows the entire building stock to be individually simulated (within the intrinsic simplifications of UBEM) without introducing further compromises in model detail. Overall, this case study demonstrates that the combination of open data and HPC-accelerated UBEM can deliver city-scale energy simulations that are both computationally tractable and sufficiently detailed to inform municipal decision-making and future digital twin applications.