This paper deals with the cost optimization of road bridges consisting of concrete slabs prepared in situ and two precast-prestressed U-shaped beams of self-compacting concrete. It shows the efficiency of four heuristic algorithms applied to a problem of 59 discrete variables. The four algorithms are the Descent Local Search (DLS), a threshold accepting algorithm with mutation operation (TAMO), the Genetic Algorithm (GA), and the Memetic Algorithm (MA). The heuristic optimization algorithms are applied to a bridge with a span length of 35 m and a width of 12 m. A performance analysis is run for the different heuristics, based on a study of Pareto optimal solutions between execution time and efficiency. The best results were obtained with TAMO for a minimum cost of 104184 €. Among the key findings of the study, the practical use of these heuristics in real cases stands out. Furthermore, the knowledge gained from the investigation of the algorithms allows a range of values for the design optimization of such structures and pre-dimensioning of the variables to be recommended.