In this paper, the structural optimization process aiming to reduce the weight of the superstructure of a five span arch bridge, built in the Province of Venice, Italy, and spanning the Piave River in the town of San Donà, is presented. The original project, with a pre-stressed concrete superstructure, was re-considered during construction because of the following two unexpected events. First, the approved new seismic national regulation became effective when the bridge was already partially built. As a result, existing foundations became unable to withstand the prescribed new seismic action. Furthermore, the Venice Water Authority, responsible for the management of the river spanned by the bridge, declared that erection phases without any provisional supports and scaffolding resting on the riverbed, as foreseen by the original project, should be preferred. Between the two possible identified design strategies able to deal with the mentioned problems, namely, the strengthening of the foundations or the lightening of the superstructure, the second option was chosen, on the basis of engineering judgement concerning the simplification of construction procedures, timing and budget. The search for the lightest possible solution, with the restraint given by the approved aesthetics of the original design and the need of keeping within the former budget, brought to the conclusion that an evolutionary structural optimization (ESO) process could be suitably applied to a composite steel and concrete superstructure.