The complex nature of crude oil distillation units, including their interactions with the associated heat recovery network and the large number of degrees of freedom, makes their optimization a very challenging task. We address here the design of a complex crude oil distillation unit by integrating rigorous tray-by-tray column simulation using commercial process simulation software with an optimization algorithm. While several approaches were proposed to tackle this problem, most of them relied on simplified models that are unable to deal with the whole complexity of the problem. The design problem is herein formulated to consider both structural variables (the number of trays in each column section) and operational variables (feed inlet temperature, pump-around duties and temperature drops, stripping steam flow rates and reflux ratio). A simulation-optimization approach for designing such a complex system is applied, which searches for the best design while accounting for heat recovery opportunities using pinch analysis. The approach is illustrated by its application to a specific distillation unit, in which numerical results demonstrate that the new approach is capable of identifying appealing design options while accounting for industrially relevant constraints.