Abstract: Paclitaxel is a potent anticancer drug widely used in the treatment of various malignancies. However, its clinical application is limited by poor aqueous solubility and low bioavailability. The present study was aimed at the formulation and evaluation of Paclitaxel-loaded solid lipid nanoparticles (SLNs) to enhance drug encapsulation, stability, and controlled release characteristics. Paclitaxel-loaded SLNs were prepared by the hot homogenization method using Glyceryl monostearate as the lipid carrier and Tween 40 and Span 80 as surfactants. Preformulation studies including organoleptic evaluation, melting point determination, solubility studies, and FTIR analysis were carried out. FTIR studies confirmed the compatibility of Paclitaxel with the selected excipients, indicating the absence of significant drug–excipient interactions. The prepared formulations were evaluated for particle size, zeta potential, entrapment efficiency, surface morphology, in vitro drug release, and stability. The particle size of the formulations ranged from 102 to 210 nm, while zeta potential values ranged from −18.4 mV to −25.8 mV, indicating good stability of the nanoparticle system. Entrapment efficiency was found to be between 72.5% and 85.6%. SEM analysis revealed that the nanoparticles were spherical in shape with smooth surface morphology and minimal aggregation. Among all formulations, F4 was identified as the optimized formulation, exhibiting a particle size of 102 nm, zeta potential of −25.8 mV, and entrapment efficiency of 85.6%. In vitro drug release studies demonstrated a sustained release profile over 8 hours, with formulation F4 showing the highest cumulative drug release of 97.55%. Stability studies conducted for 3 months under different storage conditions confirmed the stability of the optimized formulation, with all parameters remaining within acceptable limits. The results of the present study demonstrated that Paclitaxel-loaded solid lipid nanoparticles can be successfully developed as a stable and efficient drug delivery system with improved encapsulation efficiency and controlled drug release characteristics. The optimized formulation may provide enhanced therapeutic efficacy and holds promise for future anticancer drug delivery applications.