Multidrug resistance (MDR) remains a major challenge in the effective treatment of breast cancer, often leading to therapeutic failure, tumor recurrence, and poor clinical outcomes. Multiple mechanisms contribute to MDR, including overexpression of ATP-binding cassette (ABC) transporters, evasion of apoptosis, epithelial-mesenchymal transition (EMT), and the persistence of cancer stem cells (CSCs). In recent years, nanomedicine has emerged as a promising strategy to overcome these resistance pathways by enhancing drug delivery, improving intracellular drug accumulation, and enabling targeted and combination therapies.This review provides a comprehensive overview of nanomedicine-based approaches for overcoming MDR in breast cancer. Various nanocarrier systems, including liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), polymeric nanoparticles, inorganic nanocarriers, nanoemulsions, and ligand-targeted systems, are systematically discussed in terms of their design, drug delivery capabilities, and role in bypassing resistance mechanisms. Particular emphasis is placed on combination nanotherapeutic strategies, such as co-delivery of chemotherapeutic agents with natural compounds, gene modulators, or sensitizers, which have demonstrated enhanced efficacy in both in vitro and in vivo models.In addition, this review critically evaluates the limitations of current preclinical studies and highlights key challenges in clinical translation, including variability of the enhanced permeability and retention (EPR) effect, safety concerns, and large-scale manufacturing issues. Overall, nanomedicine offers a multifaceted and promising approach to overcome MDR in breast cancer; however, further translational and clinical studies are required to fully realize its therapeutic potential.
