In this paper, a practical optimization framework and enhanced strategy within an industrial setting are proposed for solving large-scale structural optimization problems in aerospace. The goal is to eliminate the difficulties associated with optimization problems, which are mostly nonlinear with numerous mixed continuous-discrete design variables. Particular emphasis is placed on generating good initial starting points for the search process and in finding a feasible optimum solution or improving the chances of finding a better optimum solution when traditional techniques and methods have failed. The efficiency and reliability of the proposed strategy were demonstrated through the weight optimization of different metallic and composite laminated wingbox structures. The results show the effectiveness of the proposed procedures in finding an optimized solution for high-dimensional search space cases with a given level of accuracy and reasonable computational resources and user efforts. Conclusions are also inferred with regards to the sensitivity of the optimization results obtained with respect to the choice of different starting values for the design variables, as well as different optimization algorithms in the optimization process.