Distillation is a critical separation process widely used in various industries, especially in petroleum refining, where efficient separation significantly influences product quality and energy consumption. This study evaluates the performance of a crude distillation unit located in Upper Egypt, with the aim of enhancing its energy and exergy efficiencies by addressing region-specific operational challenges and inefficiencies. A comprehensive thermodynamic and exergy analysis was conducted using Aspen HYSYS, based on the first and second laws of thermodynamics. The simulation model was validated against actual plant data, demonstrating strong agreement and confirming its reliability. The analysis focused on key process units, including the preflash unit, fired heater, heat exchanger network (HEN), pumps, coolers, and particularly the distillation tower, which showed the highest exergy destruction. The distillation tower alone accounted for 41.8% of total exergy destruction (44.5 GJ h⁻¹), primarily due to irreversibilities associated with phase separation. In contrast, the preflash unit exhibited high performance, with an exergy efficiency of 97.1% and minimal destruction (459 MJ h⁻¹). The fired heater and HEN also demonstrated strong efficiencies 92.7% and 91.6%, respectively, though both contributed to non-negligible thermal losses. Coolers, however, had the lowest exergy efficiency (55.2%), responsible for 33% of total exergy destruction. Parametric studies revealed that increasing overhead pressure improved overall exergy efficiency by 4.3%, while excessive pump-around flow rates led to higher irreversibilities and reduced efficiency. These findings offer valuable, localized insights for improving energy recovery and operational performance in refining processes, particularly in developing regions with limited operational data. The study supports efforts to enhance sustainability and implement energy-efficient control strategies in crude oil refining.