Here, we will emphasize Receptor Tyrosine Kinases (RTK), TKIs Therapy for HER2+ MBC, HER2-targeted TKIs are being studied in key phase 3 clinical trials in BC, TKIs and Brain Metastasis, Mechanisms of Resistance to HER2-Directed Therapies, clinical studies of HER2+ targeted TKIs, with new implications of TKIs in HER2+ MBC and nanomedicine to treat HER2+ BC. The gene discussed is ERBB2; the disease is breast cancer.