Clinical practice shows that when single-target drugs treat multi-factor diseases such as tumors, cardiovascular system and endocrine system diseases, it is often difficult to achieve good therapeutic effects, and even serious adverse reactions may occur. Multi-target drugs can simultaneously regulate multiple links of disease, improve efficacy, reduce adverse reactions, and improve drug resistance. They are ideal drugs for treating complex diseases, and therefore have become the main direction of drug development. At present, some multi-target drugs have been successfully used in many major diseases. Entrectinib is an oral small molecule inhibitor that targets TRK, ROS1, and ALK. It is used to treat locally advanced or metastatic solid tumors with NTRK1/2/3 , ROS1 and ALK gene fusion mutations. It can pass through the blood-brain barrier and is the only TRK inhibitor clinically proven to be effective against primary and metastatic brain diseases. In 2019, entrectinib was approved by the FDA to treat adult patients with ROS1-positive metastatic non-small cell lung cancer. Case reports showed that continuous administration of entrectinib was effective and tolerable. In this review, we give a brief introduction to TKK, ROS1 and ALK, and on this basis, we give a detailed and comprehensive introduction to the mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability and drug interactions of entrectinib.