Abstract: The rupture of vulnerable plaques often leads to acute coronary syndrome, causing severe cardiovascular events. Therefore, early detection of vulnerable plaques is of great significance. Molecular imaging technology, such as nuclear medicine molecular imaging, ultrasound molecular imaging, MRI and optical imaging, are used to monitor vulnerable plaques. In recent years, multimodal molecular imaging technology, providing more anatomical and biological metabolism information, has higher application value in monitoring vulnerable plaques. The preparation and construction of multimodal molecular probes are crucial for molecular imaging diagnosis of diseases. Seeking suitable targets and enhancing the targeting of molecular probes are beneficial to improve the detection rate of diseases and vulnerable plaques. Nanomaterials with special properties and advantages have been widely used in multimodal molecular probes. However, these nanoprobes are still in the preclinical research stage and are mainly used in animal models. This review focuses on the various biomarkers that appear in the histological, cellular and molecular biological changes of vulnerable plaques, and summarizes the research progress in targeted molecular imaging of multimodal nanomolecular probes in vulnerable plaques in animal models.