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.