This study presents the design and synthesis of a multifunctional nanoplatform, HN@QPS, for breast cancer chemostarvation therapy. HN@QPS is a niosome (NIO) coloaded with paclitaxel (PTX), a chemotherapeutic drug, and sodium oxamate (SO), a glycolytic inhibitor, along with quantum dots (QD) as bioimaging agents and hyaluronic acid (HA) for active targeting. The NIO were synthesized using the thin-film hydration method, and the final nanoparticles had a size of ~150 nm with a surface charge of −39.9 mV and over 90% encapsulation efficiency (EE) for PTX. The coadministration of SO with PTX significantly enhanced the anticancer effects, achieving IC50 values of 1–5 and >0.5 ppm for HN@QP and HN@QPS, respectively. HN@QPS treatment increased the apoptosis rate by more than 70% in MCF-7 breast cancer cells without significant cytotoxicity on H9F-2 normal cells. Mitochondrial fluorescence quantification and cellular uptake evaluation further confirmed the enhanced therapeutic efficacy of HN@QPS. This preliminary research highlights the potential of HN@QPS as an efficient targeted-dual drug delivery nanotheranostic for breast cancer cells.This study presents the design and synthesis of a multifunctional nanoplatform, HN@QPS, for breast cancer chemostarvation therapy. HN@QPS is a niosome (NIO) coloaded with paclitaxel (PTX), a chemotherapeutic drug, and sodium oxamate (SO), a glycolytic inhibitor, along with quantum dots (QD) as bioimaging agents and hyaluronic acid (HA) for active targeting. The NIO were synthesized using the thin-film hydration method, and the final nanoparticles had a size of ~150 nm with a surface charge of −39.9 mV and over 90% encapsulation efficiency (EE) for PTX. The coadministration of SO with PTX significantly enhanced the anticancer effects, achieving IC50 values of 1–5 and >0.5 ppm for HN@QP and HN@QPS, respectively. HN@QPS treatment increased the apoptosis rate by more than 70% in MCF-7 breast cancer cells without significant cytotoxicity on H9F-2 normal cells. Mitochondrial fluorescence quantification and cellular uptake evaluation further confirmed the enhanced therapeutic efficacy of HN@QPS. This preliminary research highlights the potential of HN@QPS as an efficient targeted-dual drug delivery nanotheranostic for breast cancer cells.