The aim of this paper is two fold. First we investigate the three different types of systems. namely cellular layout (CL), process layout (PL) and virtual cells (VCs). VCs are addressed by using family-based scheduling rule, developed by a part allocation algorithm in a PL. Simulation is used to compare three types of systems under the performance metrics such as mean flow time and mean tardiness. Results indicate that VCs have better responsiveness in terms of the performance metrics. Second we develop a new ant colony optimization-based metamodels fed by existing simulation runs to represent the prospective simulation runs, which require a lot of time and effort. Regression metamodels, which allow us to obtain much faster results, are seen to be promising to estimate the systems behaviors. (C) 2008 Elsevier Ltd. All rights reserved.