The article discusses the multifaceted role of vascular endothelial growth factor (VEGF) in cancer, beyond its well-known function in angiogenesis and vascular permeability. VEGF signaling in tumor cells, mediated by VEGF receptor tyrosine kinases (RTKs) and neuropilins (NRPs), contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumor initiation. NRPs play a crucial role in this signaling by regulating the function and trafficking of RTKs and integrins. The review highlights the importance of autocrine and paracrine VEGF signaling in tumor cells, which can occur independently of angiogenesis. This signaling is implicated in the growth, survival, migration, and invasion of cancer cells, and it is particularly important in aggressive cancers and cancer stem cell maintenance. The article also explores the therapeutic potential of targeting VEGF and NRPs, noting that while VEGF-targeted therapies like bevacizumab have shown some success, they may not fully inhibit autocrine VEGF signaling. The authors suggest that combining VEGF and NRPs targeting strategies could be more effective, especially when used in combination with other therapeutic agents.The article discusses the multifaceted role of vascular endothelial growth factor (VEGF) in cancer, beyond its well-known function in angiogenesis and vascular permeability. VEGF signaling in tumor cells, mediated by VEGF receptor tyrosine kinases (RTKs) and neuropilins (NRPs), contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumor initiation. NRPs play a crucial role in this signaling by regulating the function and trafficking of RTKs and integrins. The review highlights the importance of autocrine and paracrine VEGF signaling in tumor cells, which can occur independently of angiogenesis. This signaling is implicated in the growth, survival, migration, and invasion of cancer cells, and it is particularly important in aggressive cancers and cancer stem cell maintenance. The article also explores the therapeutic potential of targeting VEGF and NRPs, noting that while VEGF-targeted therapies like bevacizumab have shown some success, they may not fully inhibit autocrine VEGF signaling. The authors suggest that combining VEGF and NRPs targeting strategies could be more effective, especially when used in combination with other therapeutic agents.