The blood-brain barrier (BBB) and blood-tumour barrier (BTB) are critical structures that regulate the transport of substances between the bloodstream and the brain. The BBB is a specialized neurovascular unit composed of endothelial cells (ECs), pericytes, and astrocytic endfeet, which maintain brain homeostasis. However, tumours can compromise the BBB, leading to the formation of the BTB, which is more permeable but still heterogeneous in its transport properties. The BBB and BTB pose significant challenges for drug delivery to brain tumours and metastases, as they restrict the entry of therapeutic agents. Understanding the molecular and cellular components of the BBB and BTB is essential for developing strategies to improve drug delivery and treatment outcomes. The BBB is regulated by a tightly controlled neurovascular unit, with ECs, pericytes, and astrocytes working together to maintain the BBB's integrity. The BBB is disrupted during tumour progression, leading to the BTB, which is characterized by non-uniform permeability and active efflux of molecules. The BBB and BTB are influenced by various factors, including genetic and molecular profiles of the tumour, and their heterogeneity can affect drug accumulation and therapeutic efficacy. Emerging strategies, such as molecular, cellular, and physical approaches, are being explored to enhance drug delivery across the BBB and BTB, including the use of immune checkpoint inhibitors and engineered T cells. The BBB and BTB are heterogeneous, with variations in their structure and function depending on the tumour type and location. The BTB is generally considered 'leakier' than the BBB but still presents challenges for drug delivery. The BBB and BTB are influenced by various factors, including the tumour microenvironment, immune cells, and vascular changes. The BBB is a dynamic structure that can be influenced by local and systemic factors, and its integrity is crucial for maintaining brain homeostasis. Various strategies are being developed to overcome the barriers posed by the BBB and BTB, including the use of focused ultrasound (FUS) combined with microbubbles to temporarily disrupt the BBB and increase drug permeability. Other approaches include the use of stem cells for targeted drug delivery, the manipulation of EC signalling pathways to increase BBB porosity, and the use of nanoparticles to enhance drug delivery. Radiation therapy has also been shown to increase BBB/BTB permeability, although its effectiveness in improving therapeutic delivery remains a topic of ongoing research. The BBB and BTB are critical barriers that must be overcome for effective treatment of brain tumours and metastases. Understanding their structure, function, and heterogeneity is essential for developing new therapeutic strategies that can improve drug delivery and treatment outcomes. Advances in systems biology, imaging, and biomarker development are helping to identify new approaches to overcome the challenges posed by the BBB and BTB, ultimately leading to more effective treatments for brain tumours and metastases.The blood-brain barrier (BBB) and blood-tumour barrier (BTB) are critical structures that regulate the transport of substances between the bloodstream and the brain. The BBB is a specialized neurovascular unit composed of endothelial cells (ECs), pericytes, and astrocytic endfeet, which maintain brain homeostasis. However, tumours can compromise the BBB, leading to the formation of the BTB, which is more permeable but still heterogeneous in its transport properties. The BBB and BTB pose significant challenges for drug delivery to brain tumours and metastases, as they restrict the entry of therapeutic agents. Understanding the molecular and cellular components of the BBB and BTB is essential for developing strategies to improve drug delivery and treatment outcomes. The BBB is regulated by a tightly controlled neurovascular unit, with ECs, pericytes, and astrocytes working together to maintain the BBB's integrity. The BBB is disrupted during tumour progression, leading to the BTB, which is characterized by non-uniform permeability and active efflux of molecules. The BBB and BTB are influenced by various factors, including genetic and molecular profiles of the tumour, and their heterogeneity can affect drug accumulation and therapeutic efficacy. Emerging strategies, such as molecular, cellular, and physical approaches, are being explored to enhance drug delivery across the BBB and BTB, including the use of immune checkpoint inhibitors and engineered T cells. The BBB and BTB are heterogeneous, with variations in their structure and function depending on the tumour type and location. The BTB is generally considered 'leakier' than the BBB but still presents challenges for drug delivery. The BBB and BTB are influenced by various factors, including the tumour microenvironment, immune cells, and vascular changes. The BBB is a dynamic structure that can be influenced by local and systemic factors, and its integrity is crucial for maintaining brain homeostasis. Various strategies are being developed to overcome the barriers posed by the BBB and BTB, including the use of focused ultrasound (FUS) combined with microbubbles to temporarily disrupt the BBB and increase drug permeability. Other approaches include the use of stem cells for targeted drug delivery, the manipulation of EC signalling pathways to increase BBB porosity, and the use of nanoparticles to enhance drug delivery. Radiation therapy has also been shown to increase BBB/BTB permeability, although its effectiveness in improving therapeutic delivery remains a topic of ongoing research. The BBB and BTB are critical barriers that must be overcome for effective treatment of brain tumours and metastases. Understanding their structure, function, and heterogeneity is essential for developing new therapeutic strategies that can improve drug delivery and treatment outcomes. Advances in systems biology, imaging, and biomarker development are helping to identify new approaches to overcome the challenges posed by the BBB and BTB, ultimately leading to more effective treatments for brain tumours and metastases.