Cancer metastasis is responsible for more than 90% of cancer patient deaths and therapeutic options are still limited. Angiogenic vessel remodelling is an essential component of primary tumour growth, and also one of the early events of metastatic dissemination. However, targeting of angiogenic vessels to prevent or treat metastases has so far been underexplored therapeutically. Previously, we have developed a fusion compound of the cytokine LIGHT and a vascular targeting peptide (LIGHT-VTP) and shown its capability to bind to angiogenic tumour vasculature through VTP and to reverse vascular abnormality in primary insulinoma and glioblastoma without incurring vessel pruning. Here, we firstly show that LIGHT-VTP normalises vessels and enhances perfusion in primary lung cancer by inducing pericyte maturity. LIGHT-VTP-induced normalisation prevents cancer cell intravasation at the primary site, which translates into reduced circulating tumour cells in the blood and decreased metastasis in a neoadjuvant setting. Secondly, we show that LIGHT-VTP efficiently targets pathological blood vessels in the pre-metastatic niche of lungs, reducing vascular hyper-permeability and ECM deposition thus reducing circulating tumour cell extravasation and blocking metastatic lung colonization. Thirdly, we demonstrate that established mouse and human metastatic melanoma deposits are targetable by VTP. In overt mouse melanoma metastases, LIGHT-VTP normalises intra-metastatic blood vessels, increases GrzB+ effector T cells and significantly enhances survival as monotherapy. More importantly, LIGHT-VTP sensitises refractory lung metastasis to anti-PD-1 checkpoint inhibitor to augment survival rate by inducing high endothelial venules (HEVs), lymphocyte clusters and tertiary lymph node structure (TLS). Overall, these findings demonstrate an important application for LIGHT-VTP therapy in preventing metastatic development as well as exerting anti-tumour effects in established metastases.