The optimal design of gearboxes is an important factor that achieves high-performance and efficient mechanical system, and a durable product in various industries. Although most related works have used single-objective formulations and the use of stand-alone metaheuristic algorithms, such studies neglected complex interplays between structural, performance, and operational measures under realistic constraints. A new integrated layout optimization strategy by employing hybrid metaheuristic algorithms to tackle several competing objectives such as weight reduction, strengthening load-carrying capability, improving efficiency and extending fatigue life of the gearbox is presented in this paper. The developed model combines evaluation of the structural integrity, manufacturing limitations, and dynamic loading, and, therefore, is applicable in practice. Comparative analyses show good convergence performance, better resistance to local minima and ability to handle different types of gearboxes like spur, helical and planetary. In addition, the developed architecture shows a great potential for integration with Industry 4.0 processes, which will lead to optimization in real time, predictive maintenance, and efficient conceptual design methods. The demonstrated results exhibit remarkable improvements on the existing methods, and provide a strong and complete methodology on modern gearbox design applications.