Reconfigurable manufacturing systems (RMSs) are designed to manufacture a specific product, incorporating the scalability to other products in the same family. This ability is based primarily on the reconfiguration capabilities offered by reconfigurable machines tools (RMTs). This paper addresses one of the most important aspects related to the reactivity of RMSs. More specifically, it considers the relations, which link the conceived system with two important environments: its logical environment, i.e., the product family (products that share similarities) in which the RMS can evolve, and its physical environment, i.e., the physical workshop that implements this RMS. We study the machine layout problem by considering the product family evolution where two sub-problems are addressed. The first sub-problem concerns the evolution of the product, in the same family, towards new products to meet the evolutions and the requirements of the customers. The second sub-problem deals with the machine layout problem based on the results of the first sub-problem. For this, our two-phase-based approach combines the well-known metaheuristic, archived multi-objective simulated annealing (AMOSA), with an exhaustive search–based heuristic to determine the best machine layout for all the selected machines of the product family. The developed approach is based on the initially generated process plans of products (in the product family) for the RMS design under performance metrics. Moreover, the proposed layout must, at its best, respect both the constraints imposed by the generated process plans and those depicting the available location in the shop floor where machines can be placed. An illustrative numerical example is proposed to demonstrate the applicability of our approach.