Supply Chain Networks Design (SCND) is a systematic approach for ¯nding the best position and size for facilities to ensure optimal product °ow using mathematical modeling. Three ant colony-based algorithms, ACO1, ACO2, and ACO3, are used to design supply chain networks in this paper. ACO2 and ACO3 are developed based on two new pheromone trails and one heuristic trail. To measure the e®ectiveness of the proposed algorithms, a numerical study is performed on generated problem cases, and the results are compared to those obtained using LINGO. The proposed algorithms provide a signi¯cantly better solution with a di®erence of about 3.04% for ACO1, 1.78% for ACO2, and 1.65% for ACO3 on average from the exact solution and in a very short time compared to Lingo. The computational analysis shows that ACO2 and ACO3 give better results than ACO1.