Functionalized nanomaterials capable of crossing the blood-brain barrier (BBB) are critical for neurotheranostics. The BBB, composed of endothelial cells, pericytes, astrocytes, and basement membrane, regulates the exchange of substances between the brain and blood. It restricts the passage of most therapeutic agents, but nanomaterials can bypass this barrier through various mechanisms. This review discusses the anatomical structure and physiological functions of the BBB, endogenous and exogenous transport mechanisms, and the effects of nanomaterial properties on BBB permeability. It also classifies functionalized nanomaterials and provides a comprehensive review of recent advances in polymeric nanomaterials for bioimaging, therapeutics, and drug delivery. The BBB's restrictive nature poses challenges for drug delivery to the CNS, but recent developments in nanotechnology have enabled the creation of safe and effective delivery systems. The review highlights the importance of nanomaterial properties such as size, shape, charge, and surface ligands in enhancing BBB crossing. It also discusses the role of various transport mechanisms, including passive diffusion, carrier-mediated transport, adsorptive-mediated transcytosis, receptor-mediated transcytosis, and efflux pump inhibition. Additionally, exogenous methods like osmotic agents, focused ultrasound, laser, magnetic fields, and cell-mediated transcytosis are explored for temporarily increasing BBB permeability. The review concludes by emphasizing the need for further research to optimize these strategies for effective and safe drug delivery to the brain.Functionalized nanomaterials capable of crossing the blood-brain barrier (BBB) are critical for neurotheranostics. The BBB, composed of endothelial cells, pericytes, astrocytes, and basement membrane, regulates the exchange of substances between the brain and blood. It restricts the passage of most therapeutic agents, but nanomaterials can bypass this barrier through various mechanisms. This review discusses the anatomical structure and physiological functions of the BBB, endogenous and exogenous transport mechanisms, and the effects of nanomaterial properties on BBB permeability. It also classifies functionalized nanomaterials and provides a comprehensive review of recent advances in polymeric nanomaterials for bioimaging, therapeutics, and drug delivery. The BBB's restrictive nature poses challenges for drug delivery to the CNS, but recent developments in nanotechnology have enabled the creation of safe and effective delivery systems. The review highlights the importance of nanomaterial properties such as size, shape, charge, and surface ligands in enhancing BBB crossing. It also discusses the role of various transport mechanisms, including passive diffusion, carrier-mediated transport, adsorptive-mediated transcytosis, receptor-mediated transcytosis, and efflux pump inhibition. Additionally, exogenous methods like osmotic agents, focused ultrasound, laser, magnetic fields, and cell-mediated transcytosis are explored for temporarily increasing BBB permeability. The review concludes by emphasizing the need for further research to optimize these strategies for effective and safe drug delivery to the brain.