Flavonoids are a diverse class of natural polyphenolic compounds renowned for their potent anticancer, anti-inflammatory, and antioxidant activities. Despite their therapeutic potential, the clinical application of flavonoids is often limited by poor aqueous solubility, low bioavailability, rapid metabolism, and non-specific distribution, resulting in suboptimal therapeutic indices and unintended off-target effects. Recent advances in nanomedicine have provided innovative solutions to these challenges through the design of functionalized nanocarriers that enhance the delivery, stability, and efficacy of flavonoid therapeutics. This chapter focuses on advanced strategies for the targeted delivery of flavonoid-loaded nanocarriers, emphasizing the critical roles of folic acid (FA) and hyaluronic acid (HA) as ligands for active targeting. FA exploits the overexpression of folate receptors on rapidly proliferating cancer cells, whereas HA targets the CD44 receptor, which is commonly upregulated in malignant and stem-like tumor populations. We provide a detailed discussion of the molecular mechanisms underlying FA- and HA-mediated receptor recognition, cellular uptake, and intracellular trafficking. The chapter further examines methods for conjugating these ligands to diverse nanocarrier platforms, including polymeric nanoparticles, liposomes, and micelles, highlighting the advantages and limitations of each approach. Compelling in vitro and in vivo evidence is presented, demonstrating that FA- and HA-functionalized nanocarriers significantly enhance drug accumulation in tumor tissues, improve cytotoxic efficacy, and reduce systemic toxicity. Moreover, we explore the synergistic potential of co-functionalization with both FA and HA, which enables dual-receptor targeting, overcomes tumor heterogeneity, and facilitates deeper tumor penetration. Finally, the chapter considers stimuli-responsive release mechanisms and advanced dual-targeting strategies that further refine spatiotemporal control of flavonoid delivery. Overall, this comprehensive analysis underscores the promise of targeted nanocarrier functionalization in optimizing flavonoid-based therapies, offering new avenues for effective and precise anticancer treatment.