Human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor with a molecular mass of 185kDa, is overexpressed in several cancers, such as breast, gastric, ovary, prostate, and lung. HER2 is a promising target in cancer therapy because of its crucial role in cell migration, proliferation, survival, angiogenesis, and metastasis through various intracellular signaling cascades. This receptor is an ideal target for the delivery of chemotherapeutic agents because of its accessibility to the extracellular domain. In this review, we highlight different HER2-targeting strategies and various approaches for HER2-targeted delivery systems to improve outcomes for cancer therapy.