In this paper, a new genetic algorithm-based framework aimed at efficiently design multiple seismic retrofitting interventions is proposed. The algorithm focuses on the minimization of retrofitting intervention costs of reinforced concrete (RC) frame structures. The feasibility of each tentative solution is assessed by considering in an indirect way the expected annual loss (EAL), this evaluation is performed by referring to different limit states whose repairing costs are expressed as a percentage of reconstruction costs and evaluating the respective mean annual frequency of exceedance. As the EAL takes into account the overall structural performances, to involves both serviceability and ultimate limit states, two different seismic retrofitting techniques are considered. In particular, FRP wrapping of columns is employed to increase the ductility of RC elements managing life safety and collapse limit state demands. On the other hand, steel bracings are used to increase the global stiffness of the structure and mainly increase operational and damage limit states performances. The optimization procedure is carried out by the novel genetic algorithm-based framework developed in Matlab® that is connected to a 3D RC frame fiber-section model implemented in OpenSees. For both the retrofitting systems, the algorithm provides their position within the structure (topological optimization) and their sizing. Results will show that seismic retrofitting can be effectively designed to increase the overall structural safety by efficaciously optimizing the intervention costs.