Precision therapy has become an important approach in modern medicine, with the goal of providing individualized treatment according to the characteristics of individual patients. The successful development of precision medicine depends on the application of preclinical cancer models. Patient-derived organoid (PDO) xenograft models display characteristics of both PDO models and in vivo patient-derived tumor xenograft models. This type of model can not only maintain the heterogeneity of the original tumor, but also has additional advantages, such as large-scale cultivation, high-throughput drug screening in vitro and drug sensitivity testing in vivo. It is an innovative, precise preclinical disease model. In this review, we summarize the basic characteristics of the PDO xenograft model, analyze its construction method and influencing factors, further discuss its application in precision therapy, with the aim of providing a reliable preclinical experimental tool for individualized cancer treatment.