Nanostructured lipid carriers (NLCs) containing olaparib (OLA) were designed and refined to enhance effectiveness against Triple Negative Breast Cancer (TNBC) in this study. The OLA-loaded NLC formulation was prepared by melt emulsification followed by ultrasonication. The formulation optimization was performed using a Box-Behnken design in DoE. The optimized NLCs consist of Gellucire® 50/13 as the solid lipid component, Labrafac® MC 60 as the liquid lipid, and Pluronic F 127 and PEG 400 as surfactants. Characterization of the optimized formulation revealed favourable physicochemical properties, including an average particle size of 126.0 ± 4.61 nm, a polydispersity index of 0.2 ± 0.012, a zeta potential of - 13.6 ± 1.21 mV, an entrapment efficiency of 88.5 ± 5.42%, and a drug loading of 14.8 ± 2.74%. Drug release kinetics indicated that the optimized NLC system provided sustained OLA delivery, with 84.49 ± 2.2% cumulative release over 72 h, contrasting significantly with unformulated OLA, which exhibited complete release within just 24 h. Compared with plain OLA, studies using MDA-MB-231 (TNBC) cell lines revealed that the optimized olaparib-loaded NLCs produced considerably greater efficacy (p