Managing blood supply chains and network design is challenging due to product perishability, uncertain supply and demand, and blood type compatibility. We present a two-stage robust optimization model for multi-product flows of red cells, platelets, and plasma, integrating strategic facility decisions with adaptive operational allocation under white, yellow, and red scenarios. An augmented ε-constraint method uncovers cost–time trade–offs, while robust optimization guards against extreme disruptions. In this study, we use real data from Tehran’s blood transfusion organization and solve the model with CPLEX. We demonstrate that allowing substitutions compatible with the ABO blood group system and the Rhesus factor (ABO–Rh) relieves inventory pressure and reduces expected costs. The resulting Pareto frontier guides decision-makers in balancing delivery time against operating expenses.