Breast cancer is the most common disease among women and the second most common disease worldwide, accounting for 2.09 million new cases of cancer diagnosis in 2018. It accounts for 11.6% of all cancer cases and is the leading cause of cancer mortality for women as well as the fourth cause of cancer death overall. HER2-positive breast cancer is distinguished as a distinct subtype of breast cancer by the overexpression of HER2, a specific protein found on the surface of cancer cells. Because targeted medicines precisely target the overexpression of the HER2 protein, the management of HER2-positive breast cancer has undergone a complete revolution. Monoclonal antibodies targeting the extracellular domain of the HER2 protein were regarded to be a step forward in the treatment of breast cancer; however, affibody-DNA nanoparticles in particular offer a paradigm-shifting picture of cancer treatment and diagnostics. The advantages of affibody DNA nanoparticles include targeted distribution, customization, small size, potential for combination therapy, and unique character. These attributes make them a promising alternative to monoclonal antibodies, the current standard therapy, in the treatment of HER2 positive breast cancer. The purpose of this paper is to provide information on the most promising recently developed nanoparticle-based therapies for the diagnosis and management of HER-2-positive breast cancer.