The blood–brain barrier (BBB) and blood–tumour barrier (BTB) are specialized neurovascular units that regulate the transport of molecules and cells between the blood and the brain parenchyma. The BBB, formed by endothelial cells (ECs), pericytes, and astrocytic endfeet, maintains brain homeostasis by controlling the passage of substances across the blood vessel wall. Tumours disrupt the integrity of the BBB, leading to the formation of the BTB, which is characterized by heterogeneous permeability and active efflux of molecules. This review highlights the cellular and molecular components of the BBB and BTB, their impact on drug delivery, and the challenges posed by these barriers. It discusses emerging strategies to improve drug delivery across the BBB and BTB, including molecular, cellular, and physical approaches. The review also explores the role of the BBB and BTB in disease progression and treatment, particularly in the context of immunotherapy and engineered T cells. Finally, it emphasizes the importance of understanding BBB and BTB heterogeneity through single-cell sequencing and imaging techniques, as well as the development of biomarkers to assess BBB integrity, for personalized treatment strategies in primary brain malignancies and brain metastases.The blood–brain barrier (BBB) and blood–tumour barrier (BTB) are specialized neurovascular units that regulate the transport of molecules and cells between the blood and the brain parenchyma. The BBB, formed by endothelial cells (ECs), pericytes, and astrocytic endfeet, maintains brain homeostasis by controlling the passage of substances across the blood vessel wall. Tumours disrupt the integrity of the BBB, leading to the formation of the BTB, which is characterized by heterogeneous permeability and active efflux of molecules. This review highlights the cellular and molecular components of the BBB and BTB, their impact on drug delivery, and the challenges posed by these barriers. It discusses emerging strategies to improve drug delivery across the BBB and BTB, including molecular, cellular, and physical approaches. The review also explores the role of the BBB and BTB in disease progression and treatment, particularly in the context of immunotherapy and engineered T cells. Finally, it emphasizes the importance of understanding BBB and BTB heterogeneity through single-cell sequencing and imaging techniques, as well as the development of biomarkers to assess BBB integrity, for personalized treatment strategies in primary brain malignancies and brain metastases.