Glioblastoma (GBM) remains incurable due to the blood-brain barrier (BBB), tumor heterogeneity, and poor bioavailability of potent phytochemicals such as curcumin. This review analyzes a multi-strategic solution involving the nose-to-brain (N2B) route (bypassing the BBB), advanced nanocarriers (protecting phytochemicals), and surface functionalization (enabling precision targeting). We discuss how active ligands (e.g., lactoferrin), mucoadhesive polymers (e.g., chitosan), cell-penetrating peptides (e.g., TAT), and stealth modifications can transform passive carriers into guided systems. While preclinical data show superior brain targeting and survival benefits, translation is hindered by manufacturing scalability, the lack of standardized N2B protocols, and the high cost of multifunctional systems. This analysis suggests that surface-functionalized N2B nanocarriers offer a viable paradigm, provided that the field prioritizes regulatory-ready, simplified designs over complex, multi-layered platforms.