This paper addresses the two-stage supply chain network design (TS-SCND) problem with fixed costs, that models a distribution network in a supply chain that contains manufacturers, distribution centers (DCs) and retailers. We formulate the investigated problem as a mixed linear integer programming model that contains two kinds of fixed costs: ones corresponding to the distribution routes and the others corresponding to opening the DCs. In this study, our aim is to examine the characteristics of the existing metaheuristic algorithms for solving the investigated problem: four ant colony optimization algorithms and a hybrid genetic algorithm. Based on the performance comparison results, we conduct a systematic analysis of the considered solution approaches. The performed analysis points out that the hybrid genetic algorithm has the best performance regarding the count of obtained optimal solutions and the relative percentage deviations. These findings were validated through statistical analysis.