Tenofovir alafenamide has a new HPLC technology that is easy to use, precise, and accurate. An effective experimental design was carried out by thoroughly surveying all essential elements of the HPLC procedure. In accordance with ICH standards, the procedure has been validated. Optimization was performed using an analytical QbD strategy. QbD relies heavily on the Quality target product profile (QTPP). QbD ensures the quality of the pharmaceutical product for patients' protection. Based on QTPP expertise, the drug product's critical quality attribute (CQA) was determined. Three levels and three factors were utilized in the optimization process, which was carried out using a central composite design. All three variables, such as flow rate, wavelength, and mobile phase, were optimized for HPLC analysis of tenofovir alafenamide using a 23-factorial design. The compounds were separated using a C-18 column (250 mm x 4.6 mm) packed with 5.0 μm particles and equilibrated with a mobile phase (0.05%) consisting of 55 parts (v/v) methanol to 45 parts (v/v) orthophosphoric acid. The flow rate was kept constant at 0.8 ml/min, while the column temperature was kept at room temperature. The eluents were tracked using a PDA detector with a 258.0 nm wavelength setting. Good separation and peak symmetry for the drug were achieved under the following chromatographic settings. For concentrations between 10 and 50 μg/ml, the technique provided a linear response (r2 = 0.999). Repeatability, intraday accuracy, and interday precision all proved the reliability of the modified process, with percent RSDs of less than 2%. The LOQ was 0.41 μg/ml and the LOD was 0.13 μg/ml. The % recovery of spiked samples ranged from 999.69 ± 0.56 to 100.50 ± 0.47, which is within the range deemed accepTable No.. by the ICH criteria. The present approach was effectively verified for the detection of Tenofovir alafenamide in bulk drug substances and pharmaceutical dosage forms, demonstrating high selectivity, linearity, sensitivity, precision, and accuracy