Current polymer electrolyte membrane fuel cell catalyst support in a form of carbon black is linked with poor Pt utilization, non-optimized triple-phase boundary, mass transport losses, non-uniform microstructure, and durability issues. Little improvement has been made in creating a novel catalyst support microstructure and design to address the challenges associated with the use of carbon blacks. Of particular importance is the ability to control the microstructure of the catalyst layer. There is a lack of fundamental understanding of the relationship between the well-controlled catalyst layer microstructure and fuel cell performance. As catalyst layers require a structure that offers large porosity and surface area, it is envisioned that electrospun nanofibers are an excellent choice, providing a number of structural parameters that could be controlled, i.e., porosity, fiber diameter, fiber alignment, layer thickness. In this work, the fabrication parameters of electrospun carbon nanofibers (CNF) are optimized by factorial design to target key membrane electrode assembly design criterion. Validation of the structural and material properties concludes that optimized CNF surpassed design targets, achieving similar to 80% porosity, similar to 30 S cm(-1) in-plane electrical conductivity, and similar to 330 nm fiber diameter. The optimization reveals that CNF properties were successfully tailored and appear feasible as novel catalyst support. The results from the detailed and systematic design of experiments provide a basis for correlating the material and structural properties to key fuel cell performance factors.