The prevention and treatment of tumors have become a major public health priority. While surgery and chemoradiotherapy remain the cornerstone of current therapeutic strategies, they are accompanied by notable toxic side effects, which severely compromise patients’ quality of life. Flavonoids with precisely characterized molecular structures have demonstrated clinical utility in cancer treatment. Nevertheless, their therapeutic potential is hampered by inherent limitations such as poor aqueous solubility, suboptimal absorption, and chemical instability, ultimately resulting in diminished bioavailability. Recently, the synergistic combination of flavonoid compounds with nanocarrier-based delivery systems has gained prominence as a research focus, owing to its capacity for controlled release of bioactive components and site-specific targeting of tumor tissues. This study examines five flavonoids currently employed in clinical settings, reviewing the latest advancements and future directions in flavonoid-based drug delivery systems (including nanoparticles, hydrogels, and scaffolds) for anticancer applications. Additionally, we review the therapeutic applications of these five flavonoids in other prevalent diseases, proposing novel strategies to overcome the limitations of free drugs and improve therapeutic outcomes in disease management.