A facile strategy to incorporate dual sustained-release system in electrospun poly(lactic acid) (PLA) nanofibers is proposed for emerging applications in advanced drug delivery. Firstly, a model antimicrobial therapeutics, tetracycline hydrochloride (TCH) was blended with Fe3O4-COOH nanoparticles via electrostatic interaction to form novel composite nanoparticles. Then the influence of Fe3O4-COOH or TCH/Fe3O4-COOH nanoparticle incorporation on the morphology, porosity and hydrophilicity of electrospun PLA nanofiber membranes were elucidated. By studying drug release profiles, the newly designed TCH/Fe3O4-COOH/PLA nanofibrous membrane exhibited an obvious transition of drug release mechanisms from zero order release kinetics within the initial 6 days to modulated release beyond 6 days (until 14 days) in PBS. In contrast, TCH/Fe3O4-COOH and TCH/PLA nanofibrous membrane display single mechanism of burst like release within 3.5 days and 2.5 days, respectively. The Young's modulus, tensile strength and toughness of TCH/Fe3O4-COOH/PLA nanofibers are increased by 191%, 150% and 223%, respectively, compared with those of plain PLA electrospun nanofibers. Most importantly, TCH/Fe3O4-COOH/PLA nanofibrous membrane exhibited significantly stronger antibacterial activities against E. coli and S. aureus compared to TCH/Fe3O4-COOH and TCH/PLA nanofibrous membrane. The improved mechanical performance and sustained drug release behavior on TCH/Fe3O4-COOH/PLA pave the way for the emerging applications in drug delivery and tissue engineering.