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Nanotechnology empowered localized cancer chemotherapy has indicated a promising performance for targeting and controlled release of anticancer agents over a period of time to eliminate local‐regional recurrence of cancers and also to improve the tissue regeneration during/after treatment. Electrospun nanofiber‐based implantable drug‐delivery systems have been established as one of the most effective approaches for localized cancer treatment, allowing the on‐site delivery of anticancer agents and reducing systemic toxicities and side effects to normal cells. The present review aimed to summarize the latest cutting‐edge research on applications of electrospun‐based systems for local chemotherapy. Meantime, in vitro and in vivo studies conducted using various anticancer agents along with the capability of electrospun nanofibers for combinatorial/synergistic chemotherapy as well as existing challenges and the potential dramatic advances in applying this pioneering approach for clinical transition in localized treatments of cancer is also discussed. [ABSTRACT FROM AUTHOR]