<p>Superparamagnetic iron oxide nanoparticles (SPIONs) are promising in cancer nanomedicine due to their magnetic responsiveness and biocompatibility, yet their clinical use is hindered by instability, oxidation, and lack of active targeting. Here, we report a multi-stimuli-responsive nanocarrier that integrates magnetic responsiveness from the SPION core, folic acid–mediated active targeting, and pH-sensitive release. Oleic acid (OA)–stabilized SPIONs (OCION) were coated with a Brij–folic acid (BF) conjugate, and quercetin (QCT), a poorly soluble anticancer drug, was encapsulated in the hybrid lipid bilayer (HLB). The BF to OCION ratio was optimized, and the 6:1 formulation yielded uniform, monodisperse nanoparticles OCION@BF with excellent colloidal stability for 30&#xa0;days and preserved superparamagnetic properties. The optimized OCION@BF achieved 95% encapsulation efficiency and enabled sustained, pH-responsive QCT release, with faster liberation under acidic conditions. Biological assays confirmed that blank OCION@BF was non-toxic, while QCT@OCION@BF significantly improved anticancer efficacy against MCF-7 cells, showing a ~ 2.4-fold lower IC₅₀ than free QCT. Collectively, OCION@BF combines exogenous (magnetic), endogenous (folate-targeting), and microenvironmental (pH-responsive) stimuli responsiveness, representing a versatile platform for efficient delivery of poorly soluble drugs and a promising candidate for targeted cancer therapy.</p> Graphical Abstract <p></p>