​Edelfosine (EDL) and Fulvestrant (FUL), proven anticancer agents, suffer significant limitations for low water solubility and poor bioavailability. FUL is an effective breast cancer endocrine therapy (ET) as a selective estrogen receptor α (ERα) antagonist. Resistance to ET results from ER ligand-independent transactivation via PI3K-AKT and/or MAPK/ERK survival pathways that are the main target for EDL. Thus, combination of both drugs in the same nanosystem, with high encapsulation efficiency, may enhance their effectiveness, overcome undesirable features, and may overcome ET resistance. In the current work, self-assembled nanostructures of both drugs were formulated utilizing the nanoprecipitation method as stable and monodisperse nanoassemblies in aqueous suspension. The selected drug-based nanostructures were fully characterized by dynamic light scattering, FTIR spectroscopy, and transmission …​