When compared with conventional manufacturing systems, operational management of Flexible Manufacturing Systems (FMS) is generally more intrinsically difficult due to the increased complexity inherent therein. FMS are rarely fully optimised because there is a lack of readily available tools with which one may effectively evaluate and address this complexity. This work aims to apply an integrated and interactive approach using both Discrete Event Simulation (DES) and Genetic Algorithm (GA) optimisation techniques to understand and address the optimisation problems in the FMS. The chosen platform is SimEvents, selected because of the relative ease with which the complex logic in the FMS can be simulated, as well as its ability to connect to powerful MATLAB optimisation tools. A multi-machine FMS case study is modelled in this paper. The result demonstrated the integration of optimisation and simulation approach will be a more efficient and flexible tool to understand and address the problems in such complex system as FMS.