Breast cancer is the leading cancer type diagnosed among women in the world. Unfortunately, drug resistance to current breast cancer chemotherapeutics remains the main challenge for a higher survival rate. The recent progress in the nanoparticle platforms and distinct features of nanoparticles that enhance the efficacy of therapeutic agents, such as improved delivery efficacy, increased intracellular cytotoxicity, and reduced side effects, hold great promise to overcome the observed drug resistance. Currently, multifaceted investigations are probing the resistance mechanisms associated with clinical drugs, and identifying new breast cancer-associated molecular targets that may lead to improved therapeutic approaches with the nanoparticle platforms. Nanoparticle platforms including siRNA, antibody-specific targeting and the role of nanoparticles in cellular processes and their effect on breast cancer were discussed in this article.