The U.S. Annual Capital Expenditure Survey (ACES) indicates that around $192.4 billion has been spent on new facilities in the manufacturing sector, about 8% of the gross national product (GNP). Manufacturing facilities are striving to improve their plant layout, which contributes to at least a 30% reduction in operational cost. Simulation has become an essential tool in complex facility layout projects because it can incorporate many of the constraints commonly found in large-scale systems. Nevertheless, the interaction between facility planning and simulation has been inadequately understood and applied. This book addresses this problematic area using a multilevel approach designed for large-scale and complex systems. The developed methodology manages the large-scale and complex Facility Layout Problem (FLP) by considering it as a collection of subsystems that are stratified into multiple levels, sequentially created and improved.