Herein, engineered electrospun core/shell nanofibers containing different percents of Artemisinin (ART) were developed as new systems for drug administration in malaria and prostate cancer fields. In order to preserve drug bioavailability, a hyperbranched poly(butylene adipate) (HB), acting as crystal suppressant of ART, was employed as core material. Poly (vinylpirrolidone) (PVP) was selected as shell material being easy processable, self-standing and effective in facilitating ART release in aqueous medium. The investigation was carried out considering both the technological and biological aspects, by first assessing the release capability of nanofibers, and successively by evaluating the pharmacological activity of encapsulated ART against cancer cell proliferation and malarial parasites (P. falciparum) growth through in vitro tests. Inferred results confirmed the formation of nanofibers with an effective drug-loaded capability. Moreover, the different hydrophobic character of the HB and PVP enabled the triggering of the drug release and the control on its solubility in the aqueous medium.