ABSTRACT This work considers the strategic Supply Chain Network Design (SCND) problem, which is to define the number and location of facilities, and the flow of products among them to fulfilling a long-term deterministic demand. A two-phase heuristic approach was specially developed to solve large scale problems in reasonable time, extending a previous algorithm introduced in Farias et al. (2017). In the construction phase, a multi-start approach was developed to generate diversified initial solutions from each new iteration of a layered-based rounding heuristic. In the second phase, a local search heuristic improves the solution provided by the rounding method. The solution method is evaluated using randomly generated instances, and a evaluated strategic of marketing in a real case study applied to a company to redesigning the supply chain to two lines of products.The obtained results evidence the effectiveness and flexibility of the developed approach for handling very large instances.