Metamodels are models of simulation models. Metamodels are able to estimate the simulation responses corresponding to a given combination of input variables. A simulation metamodel is easier to manage and provides more insights than simulation alone. Traditionally, the multiple regression analysis is utilized to develop the metamodel from a set of simulation experiments. Simulation can consequentially benefit from the metamodelling in post-simulation analysis. A backpropagation (BP) neural network is a proven tool in providing excellent response predictions in many application areas and it outperforms regression analysis for a wide array of applications. In this paper, a BP neural network is used to generate metamodels for simulated manufacturing systems. For the purpose of optimal manufacturing systems design, mathematical models can be formulated by using the mapping functions generated from the neural network metamodels. The optimization model is then solved by a stochastic local search approach, simulated annealing (SA), to obtain an optimal configuration with respect to the objective of the systems design. Instead of triggering the detailed simulation programs, the SA-based optimization procedure evaluates the simulation outputs by the neural network metamodels. By using the SA-based optimization algorithm, the solution space of the studied problem is extensively exploited to escape the entrapment of local optima while the number of time consuming simulation runs is reduced. The proposed methodology is illustrated to be both effective and efficient in solving a manufacturing systems design problem through an example.