Oral administration of hydrophobic antineoplastic drugs is frequently hampered by poor aqueous solubility, extensive first-pass hepatic metabolism, and low gastrointestinal bioavailability. This pharmaceutical study develops, optimizes, and evaluates surface-modified Nanostructured Lipid Carriers (NLCs) engineered for the enhanced oral bioavailability and controlled intestinal release of paclitaxel. The lipid nanoparticles were synthesized via high-pressure hot homogenization utilizing solid and liquid lipid matrices stabilized with non-ionic surfactants and functionalized with chitosan for mucoadhesive targeting. Physicochemical characterization demonstrated uniform spherical morphology with a mean hydrodynamic particle size of 138.4 nanometers, polydispersity index of 0.142, and high drug entrapment efficiency of 92.6%. In vivo pharmacokinetic studies conducted in rodent models confirmed a 4.6-fold enhancement in systemic peak plasma concentration (Cmax) and a 5.2-fold increase in total area under the plasma concentration-time curve (AUC0-inf) compared to standard oral drug suspensions. Cellular cytotoxicity assays against human carcinoma cell lines corroborated enhanced cellular uptake and apoptotic induction, establishing the formulated NLCs as a promising nanocarrier platform for oral cancer chemotherapy.