Lymph node metastasis is an indicator of the invasiveness and aggressiveness of cancer. It is a vital prognostic factor in clinical staging of the disease and therapeutic decision-making. Patients with positive metastatic lymph nodes are likely to develop recurrent disease, distant metastasis, and succumb to death in the coming few years. Lymph node dissection and histological analysis are needed to detect whether regional lymph nodes have been infiltrated by cancer cells and determine the likely outcome of treatment and the patient's chances of survival. However, these procedures are invasive, and tissue biopsies are prone to sampling error. In recent years, advanced molecular imaging with novel imaging probes has provided new technologies that are contributing to comprehensive management of cancer, including non-invasive investigation of lymphatic drainage from tumors, identifying metastatic lymph nodes, and guiding surgeons to operate efficiently in patients with complex lesions. In this review, first, we outline the current status of different molecular imaging modalities applied for lymph node metastasis management. Second, we summarize the multi-functional imaging probes applied with the different imaging modalities as well as applications of cancer lymph node metastasis from preclinical studies to clinical translations. Third, we describe the limitations that must be considered in the field of molecular imaging for improved detection of lymph node metastasis. Finally, we propose future directions for molecular imaging technology that will allow more personalized treatment plans for patients with lymph node metastasis.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.