Featured Application: An optimization method, based on Simulated Annealing, is developed for the design of reinforced concrete slab.Abstract: Flat slabs have several advantages such as a reduced and simpler formwork, versatility, and easier space partitioning, thus making them an economical and efficient structural system. When producing structural components in series, every detail can lead to significant cost differences. In these cases, structural optimization is of paramount relevance. This paper reports on the structural optimization of reinforced concrete slabs, presenting the case of a rectangular slab with two clamped adjacent edges and two simply supported edges. Using the yield lines method and the principle of virtual work, a cost function can be formulated and optimized using simulated annealing (SA). Thus, the optimal distribution of reinforcing bars and slab thickness can be found considering the flexural ultimate limit state and market materials costs. The optimum result was defined by the orthotropic coefficient k = 8, anisotropic coefficient g = 1.4, and slab thickness H = 11.8 cm. A sensitivity analysis of the solution was developed considering different material costs.