The pre-metastatic niche (PMN) is a critical microenvironment that facilitates the spread of cancer cells to distant organs. This review explores the formation, characteristics, and therapeutic implications of the PMN, emphasizing the roles of tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells in shaping the metastatic niche. The PMN is characterized by immunosuppression, enhanced vascular permeability, and angiogenesis, which are essential for tumor cell settlement and proliferation. The PMN is established through the interaction of primary tumor-derived factors, tumor-mobilized bone marrow-derived cells (BMDCs), and the local stromal microenvironment of prospective metastatic organs. Key cellular components include macrophages, neutrophils, MDSCs, and T/B cells, while molecular factors such as secreted substances from tumors and extracellular vesicles contribute to the PMN formation. The PMN is influenced by processes such as epithelial-mesenchymal transition (EMT), immunosuppression, extracellular matrix (ECM) remodeling, metabolic reprogramming, vascular permeability, and angiogenesis. The PMN varies across different metastatic organs, such as lymph nodes, lungs, liver, brain, and bones. Therapeutic approaches targeting the PMN, including signaling pathways like TGF-β, VEGF, and MET, are highlighted. The PMN plays a crucial role in cancer metastasis by providing a supportive environment for tumor cell colonization and growth. Understanding the PMN's dynamics is essential for developing effective therapeutic strategies to combat tumor metastasis.The pre-metastatic niche (PMN) is a critical microenvironment that facilitates the spread of cancer cells to distant organs. This review explores the formation, characteristics, and therapeutic implications of the PMN, emphasizing the roles of tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells in shaping the metastatic niche. The PMN is characterized by immunosuppression, enhanced vascular permeability, and angiogenesis, which are essential for tumor cell settlement and proliferation. The PMN is established through the interaction of primary tumor-derived factors, tumor-mobilized bone marrow-derived cells (BMDCs), and the local stromal microenvironment of prospective metastatic organs. Key cellular components include macrophages, neutrophils, MDSCs, and T/B cells, while molecular factors such as secreted substances from tumors and extracellular vesicles contribute to the PMN formation. The PMN is influenced by processes such as epithelial-mesenchymal transition (EMT), immunosuppression, extracellular matrix (ECM) remodeling, metabolic reprogramming, vascular permeability, and angiogenesis. The PMN varies across different metastatic organs, such as lymph nodes, lungs, liver, brain, and bones. Therapeutic approaches targeting the PMN, including signaling pathways like TGF-β, VEGF, and MET, are highlighted. The PMN plays a crucial role in cancer metastasis by providing a supportive environment for tumor cell colonization and growth. Understanding the PMN's dynamics is essential for developing effective therapeutic strategies to combat tumor metastasis.