Scheduling problems have been extensively investigated in the past half century due to its essential role in manufacturing environments and different service sectors. Efficient allocation of resources supported with the appropriate sequencing has been considered to be major mathematical optimization problem. Simulation is a very powerful tool, which is used to describe and illustrate very complex production systems. Yet, integrating an optimization method in a simulation model, which could propose a near optimal production schedule, will facilitate a flexible and effective controlling of the shop floor. In this work, a hybrid flow shop scheduling problem in the production of semiconductor will be analyzed. Multiple objective functions are conducted, namely the minimization of makespan and the total tardiness. An integrated simulation-based optimization approach will be developed to solve the problem.