Doxorubicin (DOX) and folic acid (FA) were incorporated into the UiO-66 metal organic framework (MOF) and following were loaded into the carboxymethyl chitosan/poly ethylene oxide (PEO)/polyurethane core-shell nanofibers for controlled release of DOX and FA toward MCF-7 cells death. The synthesized nanocarriers were characterized using TEM, XRD, and SEM analysis. The drug loading efficiency and release profiles of DOX/MOF and FA/MOF from synthesized nanofibers have been investigated. The fitting of kinetic data by the pharmacokinetic models demonstrated the non-Fickian diffusion from nanofibers and Fickian diffusion from core-shell fibers. The cytotoxicity of synthesized nanofibers toward MCF-7 cancer cells was evaluated using DAPI staining, MTT assay and flow cytometry tests to investigate the simultaneous use of DOX and FA in the nanofibrous matrix for MCF-7 cells death in vitro. The maximum cell death using DOX-FA loaded-core-shell fibers produced by coaxial electrospinning method under 0.3, 0.5 and 0.8 mLh shell flow rates were found to be 82 ± 0.7, 83 ± 0.5 and 87 ± 0.5% after 168, 240 and 240 h, respectively. The cytotoxicity results indicated that the co-delivery of DOX and FA into the core-shell fibers could be widely used for various cancers treatment.