This paper presents a general mathematical programming formulation to determine the optimal operating conditions to synthesize nanofibers through an electrospinning process at minimum cost. Several relationships based on experimental data for different polymers to determine the nanofiber diameter and costs are proposed. Also, a general optimization approach is proposed to trade off the relationships between cost and nanofiber diameter. A case study including the specific relationships for three polymers and five operating conditions is presented. The proposed approach is general, and it can be applied to different cases.