Manufacturing firms must meet a wide variety of customer needs flexibly and effectively. Thus, simultaneous design of the product family and the supply chain network is required. This design problem must be assessed in terms of strategic-level decision making under uncertainties without any detailed and fixed information on the design conditions. We therefore propose a mathematical framework by considering the optimal profitability and robustness against destructive incidences. This paper discusses the design problem structure and formulates it as a mixed-integer programming problem. A computational method is configured for solving the optimization problem, in which only profitability is considered as the objective. A procedure to assess the robustness of the profitability-oriented optimal solution is proposed by evaluating the Pareto optimality among the nominal optimal solution and its competitive solutions. A case study of a coffee maker product family design problem is demonstrated to verify the proposed framework.