This study aimed to enhance the solubility and bioavailability of Nifedipine through the formulation and optimization of self-emulsifying drug delivery systems (SEDDS). The solubility of Nifedipine in various excipients was investigated, with Capmul MCM, Tween 80, and PEG 400 selected as the oil phase, surfactant, and co-surfactant, respectively, due to their high solubilization capacities. A pseudo ternary phase diagram was constructed to identify the optimal composition for self-emulsification. Formulation optimization using Central Composite Design (CCD) resulted in the identification of an optimized formulation (F4) based on parameters such as globule size, transmittance, emulsification time, and drug release. The prepared S-SEDDS formulation was converted into solid dosage form tablets, with various evaluation parameters assessed to ensure tablet quality. Different methods for Nifedipine extraction were evaluated, and the most efficient method was selected based on recovery percentage. Pharmacokinetic analysis of plasma concentration-time profiles provided insights into drug absorption, distribution, metabolism, and excretion. Finally, the performance of the formulated S-SEDDS tablets was compared with marketed tablets, assessing parameters such as AUC, Cmax, and Tmax to evaluate bioavailability and efficacy. Overall, this study offers valuable insights into optimizing S-SEDDS for Nifedipine delivery, contributing to enhanced solubility and bioavailability.