The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1 play crucial roles in inflammation-induced angiogenesis and tumorigenesis. CX3CL1 has unique properties, combining chemoattractant and adhesion molecule functions. The soluble form (sFKN) attracts T cells and monocytes, while the membrane-bound form (mFKN) facilitates diapedesis and cell-to-cell adhesion, particularly between leukocytes and activated endothelial cells. FKN signaling through CX3CR1 is essential in various inflammatory and immune processes. FKN is strongly upregulated in hypoxic conditions and inflammatory cytokine release, acting as a key angiogenic factor in the tumor microenvironment. The FKN/CX3CR1 axis influences cell adhesion, apoptosis, and migration, contributing to tumor progression and metastasis. This review highlights the role of the FKN signaling pathway in angiogenesis, inflammation, and cancer, discussing the mechanisms that determine its pro- or anti-tumor effects.The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1 play crucial roles in inflammation-induced angiogenesis and tumorigenesis. CX3CL1 has unique properties, combining chemoattractant and adhesion molecule functions. The soluble form (sFKN) attracts T cells and monocytes, while the membrane-bound form (mFKN) facilitates diapedesis and cell-to-cell adhesion, particularly between leukocytes and activated endothelial cells. FKN signaling through CX3CR1 is essential in various inflammatory and immune processes. FKN is strongly upregulated in hypoxic conditions and inflammatory cytokine release, acting as a key angiogenic factor in the tumor microenvironment. The FKN/CX3CR1 axis influences cell adhesion, apoptosis, and migration, contributing to tumor progression and metastasis. This review highlights the role of the FKN signaling pathway in angiogenesis, inflammation, and cancer, discussing the mechanisms that determine its pro- or anti-tumor effects.