<p>Combined dosages offer several advantages over single dosages, including fewer pills to take daily, simplified regimens, and enhanced therapeutic effects. Therefore, a straightforward, selective, and fast reversed-phase HPLC method has been established and validated for the simultaneous analysis of Esomeprazole and Ketorolac tromethamine in a combined dosage form. There was no interference with diluents, and the procedure was specific. The average recovery rates for Esomeprazole and Ketorolac Tromethamine are 99.96% and 99.934%, respectively. The suggested approach was accurate and precise, with the system precision having a percentage RSD of 0.09%, the assay precision a percentage RSD of 0.21%, and an intermediate precision of 0.43%. The correlation coefficient was found to be 0.998 from a linearity study, indicating that the method was linear over the range of 40%, 80%, 100%, 120%, and 160%. Under all degradation conditions, there was no interference at the retention time of the Ketorolac Tromethamine and Esomeprazole peaks, and the peak purity index met compliance. Drugs can be degraded through acid hydrolysis and oxidation; however, these processes do not affect the method. The approach was found to be resilient to potential modifications. To determine the quality of the drug substance during routine analysis with consistent and repeatable results in combined dose formulations, the proposed method is not only practical and reliable but also environmentally sustainable, making it a more effective solution for analyzing Esomeprazole and Ketorolac Tromethamine.</p>