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Cancer therapy has achieved new heights with numerous advancements made in this field still, cancer treatment modalities including chemotherapy, radiotherapy, immunotherapy, neoadjuvant therapy, and surgery have limitations in clinics and urges for new therapeutics. Natural products remain the mainstay of chemotherapy since ancient times. Flavonoids are a class of readily available polyphenolic secondary plant metabolites with remarkable anti-cancerous properties. However, poor aqueous solubility, rapid clearance from the blood, and poor bioavailability hinder their clinical use. In this direction, advancements in nanoparticle synthesis and functionalization have produced nanoscale drug delivery agents affording safe and target-specific delivery. Here, we highlight the importance of nanotechnology in safely delivering flavonoids to tumor tissues with high efficiency. We have also described the advancement of flavonoid-loaded nanoparticles either single or in combination with a conventional chemotherapeutic in pre-clinical settings which distinguishes them from other chemotherapeutics. While enormous pre-clinical studies have been published on flavonoid-based nanoparticles the emphasis here is to push these nanomedicines into clinical studies which are likely to influence clinical investigations and their translation for the treatment of cancer patients.