The article presents a decision support methodology for the selection of a modular reconfigurable assembly system using three-dimensional visualization, component-based simulation, efficiency, and economic analysis methodology. During the design and selection of an assembly system, measurement schemes should be established for determining and understanding design effectiveness. Measurements can be classed into two categories: cost and performance. Understanding assembly production costs is the first step towards increasing profits. The authors have developed an analysis method that integrates factory simulation, overall equipment efficiency (OEE), and economic analysis methods. Cost calculation includes life cycle cost (LCC), cost of ownership (COO), commonly used investment evaluation methods, discounted cash flow techniques, net present value (NPV), and internal rate of return (IRR). The idea is to use these integrated analysis methods in the selection and development of a light assembly system. The development is based on selected industrial standards and the authors’ own experience in assembly system design and simulation. The developed TCO (total cost of ownership) methodology is useful in system supplier and end-user communication; ideally, it is used in the assembly system sales process, it helps in trade-off analysis of the system concepts, and it improves system specification.