Abstract: HER2 is not only a predictor of targeted therapy but also a definite prognostic factor. HER2-positive tumors are high-malignant, strong aggressive, with early metastasis and recurrence and poor prognosis. Therefore, accurate evaluation of HER2 status in cancer patients is the key to improve the efficacy, and it is crucial to clarify the HER2 status in vivo. However, HER2 status is highly heterogeneous during targeted therapy. The classical methods such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) cannot monitor the expression of HER2 in vivo, real time or dynamically and cannot accurately locate. It is difficult to meet the requirements of early diagnosis, treatment and precise treatment of malignant tumors with high HER2 expression. With the rapid development of molecular imaging, molecular probes could evaluate the effect of tumor immunotherapy quickly, accurately, noninvasively and effectively, and the probes play a critical role in solving the problem of tumor heterogeneity. Based on the existing HER2 molecular probes, this review analyzes the progress of molecular imaging-guided targeted therapy.