This review delves into the formation and characteristics of the pre-metastatic niche (PMN), a critical environment that facilitates the spread of cancer cells to distant organs. The PMN is shaped by tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells, along with cellular elements such as macrophages, neutrophils, bone marrow-derived suppressive cells, and T/B cells. Key mechanisms include epithelial-mesenchymal transition (EMT), immunosuppression, extracellular matrix (ECM) remodeling, metabolic reprogramming, and angiogenesis. The review highlights the role of various signaling pathways, such as TGF-β, VEGF, and MET, and discusses therapeutic approaches targeting these components to combat tumor metastasis. Understanding the dynamics of the PMN is crucial for developing effective strategies to prevent and treat metastatic disease.This review delves into the formation and characteristics of the pre-metastatic niche (PMN), a critical environment that facilitates the spread of cancer cells to distant organs. The PMN is shaped by tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells, along with cellular elements such as macrophages, neutrophils, bone marrow-derived suppressive cells, and T/B cells. Key mechanisms include epithelial-mesenchymal transition (EMT), immunosuppression, extracellular matrix (ECM) remodeling, metabolic reprogramming, and angiogenesis. The review highlights the role of various signaling pathways, such as TGF-β, VEGF, and MET, and discusses therapeutic approaches targeting these components to combat tumor metastasis. Understanding the dynamics of the PMN is crucial for developing effective strategies to prevent and treat metastatic disease.