This study presents a multifunctional nanotheranostic system, HN@QPS, composed of niosomes (NIO) co-loaded with paclitaxel (PTX), a chemotherapeutic drug for breast cancer, and sodium oxamate (SO), a glycolytic inhibitor, along with quantum dots (QD) for bioimaging and hyaluronic acid (HA) for active targeting. The NIOs were synthesized using the thin-film hydration method and exhibited a size of approximately 150 nm and a surface charge of -39.9 mV, with over 90% entrapment efficiency for PTX. The co-delivery of SO with PTX significantly enhanced the anticancer effects of PTX, 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 HHF-2 normal cells. The study also demonstrated efficient toxicity against MCF-7 cells and improved uptake of HN@Q in MCF-7 cells. The results indicate that HN@QPS has potential as an efficient targeted dual drug delivery nanotheranostic for breast cancer. The system combines chemotherapy with imaging and targeting capabilities, offering a promising approach for cancer therapy.This study presents a multifunctional nanotheranostic system, HN@QPS, composed of niosomes (NIO) co-loaded with paclitaxel (PTX), a chemotherapeutic drug for breast cancer, and sodium oxamate (SO), a glycolytic inhibitor, along with quantum dots (QD) for bioimaging and hyaluronic acid (HA) for active targeting. The NIOs were synthesized using the thin-film hydration method and exhibited a size of approximately 150 nm and a surface charge of -39.9 mV, with over 90% entrapment efficiency for PTX. The co-delivery of SO with PTX significantly enhanced the anticancer effects of PTX, 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 HHF-2 normal cells. The study also demonstrated efficient toxicity against MCF-7 cells and improved uptake of HN@Q in MCF-7 cells. The results indicate that HN@QPS has potential as an efficient targeted dual drug delivery nanotheranostic for breast cancer. The system combines chemotherapy with imaging and targeting capabilities, offering a promising approach for cancer therapy.