This paper presents a framework of intelligent manufacturing scheduling and control with specific applications to operations of rail-guided vehicle systems (RGVS). A RGVS control architecture is discussed with a focus on a simulated experiment in operations of the load/unload area of a real industrial flexible manufacturing system (FMS). In the operation stage of a material handling system (MHS), all shop floor data are subject to change as time goes. These data can be collected using a data acquisition device and stored in a dynamic database. The RGVS simulator used in this experimental study is designed to incorporate some possible situations representing existing material handling scenarios in order to evaluate alternative control policies. At the development stage of the controller, all possible combinations of most commonly encountered scenarios such as RGV failures, production schedule changes, machine breakdowns, and rush orders are to be simulated and corresponding results collected. The data are then structured into training data pairs to properly train an artificial neural network. The neural network, trained by using input/output data sets obtained from a number of simulation runs, will then provide control strategy recommendations. At the application stage, whenever an abnormal scenario occurs, a pre-processor will be activated to pre-screen and prepare an input vector for the trained neural network. If such an abnormal scenario falls outside the existing domain of data sets employed to train the neural network, as judged by the MHS supervisory controller, an off-line training module will be activated to eventually update the neural network. The recommended control strategies will be transmitted to the MHS control for real-time execution. If there is no further abnormal event detected, the dynamic data base (DDB) module simply continues to monitor the MHS activities. The proposed MHS control system combines the features of example based neural network technology and simulation modeling for true intelligent, on-line, pseudo real-time control. Not only will the system assure that feasible material handling control actions be taken, but also it will implement better control decisions through continuous learning from experiences captured as the operation time of the MHS accumulates.