VEGF, a key player in cancer, extends beyond angiogenesis and vascular permeability to influence tumour cell functions, including cancer stem cell activity and tumour initiation. VEGF signals in tumour cells are mediated by VEGF receptors (VEGFRs) and neuropilins (NRPs), which regulate receptor function and integrin activity. VEGF receptors, such as VEGFR1, VEGFR2, and VEGFR3, are expressed in various tumour types, with VEGFR2 being crucial for angiogenesis. NRPs, though primarily co-receptors, can function as VEGF receptors, enhancing VEGF signalling and contributing to tumour progression. NRPs also interact with other receptors, such as MET, EGFR, and TGFβ receptors, influencing tumour cell functions like invasion, proliferation, and survival. VEGF signalling can be autocrine or paracrine, with autocrine signals playing a significant role in tumour initiation and cancer stem cell maintenance. VEGF signalling in tumour cells is regulated by factors like hypoxia, which activates HIF and promotes VEGF expression. NRPs are involved in VEGF signalling and can influence tumour cell behaviour through interactions with integrins and other receptors. Targeting VEGF and its receptors, including NRPs, is a promising therapeutic approach, though challenges remain, such as resistance and off-target effects. Preclinical studies suggest that targeting NRPs or VEGF–NRP interactions could be effective, especially in combination with VEGF inhibitors like bevacizumab. However, the role of NRPs in cancer remains complex, with implications for therapy and tumour biology. Understanding VEGF signalling in tumour cells is crucial for developing more effective therapeutic strategies.VEGF, a key player in cancer, extends beyond angiogenesis and vascular permeability to influence tumour cell functions, including cancer stem cell activity and tumour initiation. VEGF signals in tumour cells are mediated by VEGF receptors (VEGFRs) and neuropilins (NRPs), which regulate receptor function and integrin activity. VEGF receptors, such as VEGFR1, VEGFR2, and VEGFR3, are expressed in various tumour types, with VEGFR2 being crucial for angiogenesis. NRPs, though primarily co-receptors, can function as VEGF receptors, enhancing VEGF signalling and contributing to tumour progression. NRPs also interact with other receptors, such as MET, EGFR, and TGFβ receptors, influencing tumour cell functions like invasion, proliferation, and survival. VEGF signalling can be autocrine or paracrine, with autocrine signals playing a significant role in tumour initiation and cancer stem cell maintenance. VEGF signalling in tumour cells is regulated by factors like hypoxia, which activates HIF and promotes VEGF expression. NRPs are involved in VEGF signalling and can influence tumour cell behaviour through interactions with integrins and other receptors. Targeting VEGF and its receptors, including NRPs, is a promising therapeutic approach, though challenges remain, such as resistance and off-target effects. Preclinical studies suggest that targeting NRPs or VEGF–NRP interactions could be effective, especially in combination with VEGF inhibitors like bevacizumab. However, the role of NRPs in cancer remains complex, with implications for therapy and tumour biology. Understanding VEGF signalling in tumour cells is crucial for developing more effective therapeutic strategies.