A functional vascular system is indispensable for drug delivery and fundamental for responsiveness of the tumour microenvironment to such medication. At the same time, the progression of a tumour is defined by the interactions of the cancer cells with their surrounding environment, including neovessels, and the vascular network continues to be the major route for the dissemination of tumour cells in cancer, facilitating metastasis. So how can this apparent conflict be reconciled? Vessel normalisation—in which redundant structures are pruned and the abnormal vasculature is stabilised and remodelled—is generally considered to be beneficial in the course of anti-cancer treatments. A causality between normalised vasculature and improved response to medication and treatment is observed. For this reason, it is important to discern the consequence of vessel normalisation on the tumour microenvironment and to modulate the vasculature advantageously. This article will highlight the challenges of controlled neovascular remodelling and outline how vascular normalisation can shape disease management.