Background and purpose: Myricetin (3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one) is a polyhydroxyfavonol compound widely found in nature has been shown to possess anticancer effects in various cancers. Despite its efficacy, poor water solubility and low oral bioavailability hinders its therapeutic application. To overcome these limitations, Nanoemulsion (NE) emerged as a promising approach that combines the advantages of NE into a single delivery system. The present study aimed to investigate the advantage of myricetin loaded NE over and above native Myricetin. Experimental Approach: The nano-emulsion was formulated using Capryol 90 as oil, Tween 20 as a surfactant, and Transcutol HP as a co-surfactant. Further comparative analysis of Myricetin and nano-emulsified Myricetin (Myr-NE) were carried out in triple negative breast cancer (MDA-MB-231) cells for anticancer activity. Key results: The optimized Myr-NE had a zeta potential of -6.35±0.3, an average particle size of 89.32±2.8 nm, PDI of 0.105±0.02, and a spherical shape as confirmed in transmission electron microscopy. Diffusion-dominant drug release was observed with 95.49±2.84 % Drug release for 24hrs, 2-fold higher than Myr-suspension. When nano-emulsified, Myricetin exhibited efficient inhibition of cell proliferation, clonogenicity, and increased apoptosis with IC50 of 37 µM, a dose ~2.5 fold lower than native Myricetin. Mechanistic insights reveal that Myr-NE induced more ROS generation and considerably inhibited AKT and mTOR activation, leading to enhanced anticancer activity. Conclusions & Implications: In conclusion, these findings suggest that the therapeutic efficacy of Myricetin significantly improved through a novel Myr-NE formulation which may be a promising therapeutic approach for treating TNBC.