The systemic administration of immunotherapy faces significant limitations, including inadequate anti-tumor immune responses and undesirable side effects. To overcome these challenges, localized drug delivery platforms have emerged as a promising strategy to enhance therapeutic efficacy by increasing direct tumor exposure to immunotherapeutic agents while minimizing off-target toxicity. This study presents the design, fabrication, and functional evaluation of a biodegradable Nanofluidic Drug Eluting Seed (bNDES)—a polymer-based intratumoral drug delivery system. The bNDES is composed of FDA-approved biodegradable polymers, Poly(ε-caprolactone) (PCL) and Poly(D, L-lactic-co-glycolic acid) (PLGA), forming a nanofibrous scaffold tailored for intratumoral therapeutic interventions. The fabrication process resulted in microporous and nanofibrous implants with minimal defects and bead formation.