The present research work entails the development and validation of a simple, robust and sensitive stability indicating reverse phase high performance liquid chromatographic method using Quality by Design methodology for estimation of Tenofovir alafenamide fumarate in bulk drug and its marketed dosage form. Chromatographic separation was performed in isocratic mode using Inertsil C18 column, mobile phase composed of Acetonitrile: ammonium formate buffer pH 5(40: 60) at a flow rate of 1mL/min with Photo Diode Array (PDA) detection at 261nm. A Box-Behnken statistical design with 3 factors and 3 levels was selected for the optimization study. Interaction effects of Critical Quality Parameters (Buffer pH, Organic Phase-% acetonitrile, flow rate) were evaluated for critical quality attributes (Retention time, NTP and symmetry factor). The optimized method was validated according to the current International Conference Harmonization (ICH) Q2 R1 guidelines. The method was found to be linear, covering the range from 1.5 μg/mL – 4.5 μg/mL with correlation coefficient r2 of 0.9996 and precision was found to be less than 2%. Limit of Detection and Limit of Quantification was found to be 1µg/mL and 1.2µg/mL respectively. Accuracy was between 99% and 102%. Forced degradation study was conducted under degradation conditions like light, oxidation, dry heat, acidic, basic, hydrolysis in order to establish the intrinsic stability of molecule. The method was successfully applied for the determination of the drug in commercial dosage form. This holistic stability indicating chromatographic method focused on QbD approach ensured reproducibility and was found to be useful for routine analysis of Tenofovir alafenamide fumarate.