The objective of this study was to apply simulation and genetic algorithms for the economic and environmental optimization of the reverse network (manufacturers, waste managers, and recyclers in Sao Paulo, Brazil) of waste from electrical and electronic equipment (WEEE) to promote the circular economy. For the economic evaluation, the reduction in fuel, drivers, insurance, depreciation, maintenance, and charges was considered. For the environmental evaluation, the impact of abiotic, biotic, water, land, air, and greenhouse gases was measured. It was concluded that the optimized structure of the WEEE reverse chains for Sao Paulo, Brazil provided a reduction in the number of collections, thus making the most of cubage. It also generated economic and environmental gains, contributing to the strategic actions of the circular economy. Therefore, the proposed approach is replicable in organizational practice, which is mainly required to meet the 2030 agenda of reducing the carbon footprint generated by transport in large cities. Thus, this study can guide companies in structuring the reverse WEEE chains in Sao Paulo, Brazil, and other states and countries for economic and environmental optimization, which is an aspect of great relevance considering the exponential generation of WEEE.