This study concerns with the design optimization of steel skeletal structures thereby utilizing both a real-life specification provisions and ready steel profiles named hot-rolled I sections. For this purpose, the enhanced genetic algorithm methodology named EGAwMP is utilized as an optimization tool. The evolutionary search mechanism of EGAwMP is constituted on the basis of generational genetic algorithm (GGA). The exploration capacity of EGAwMP is improved in a way of dividing an entire population into sub-populations and using of a radial basis neural network for dynamically adjustment of EGAwMP’s genetic operator parameters. In order to improve the exploitation capability of EGAwMP, the proposed neural network implementation is also utilized for prediction of more accurate design variables associating with a new design strategy, design codes of which are based on the provisions of LRFD_AISC V3 specification. EGAwMP is applied to determine the real-life ready steel profiles for the optimal design of skeletal structures with 105, 200, 444, and 942 members. EGAwMP accomplishes to increase the quality degrees of optimum designations Furthermore, the importance of using the real-life steel profiles and design codes is also demonstrated. Consequently, EGAwMP is suggested as a design optimization tool for the real-life steel skeletal structures.