Orally Disintegrating Tablets (ODTs) are solid dosage forms that rapidly disintegrate or dissolve to release the drug upon contact with saliva in the mouth. As these tablets require special attention during formulation design, it is necessary to use advanced control and formulation design techniques to increase the quality. Quality by Design (QbD) was defined as an approach including better scientific understanding of critical process and product attributes, designing controls and tests based on scientific understanding limits during development stage and used to work in an environment for continuous improvement of information obtained during the product lifecycle. The aim of the study was to develop an ODT formulation containing Metoprolol tartrate with appropriate features via QbD approach with the help of artificial intelligence programs to enlight the multivariate relations between critical parameters and quality attributes of on final product and to obtain an optimum formulation. Physical and chemical tests were conducted on tablets prepared by direct compression according to the designated formulation and process variables. Then, experimental data was evaluated with modeling programs use artificial intelligence technique, FormRules V3.32 to understand the relationship between independent input variables and the critical quality attributes; later with INForm V5.1 for optimization. The optimized formula was prepared and according to test results tablets shows compliance with the pharmacopoeia limits. The adoption of QbD approach and usage of artificial intelligence programs has increased the efficiency of the formulation development process with better understanding of the product and process.