Hypertension affects approximately 1.28 billion adults globally, with significant prevalence in low and middleincome countries. Metoprolol, a beta-blocker, effectively treats hypertension and other cardiovascular conditions but requires multiple daily doses due to its short half-life, leading to compliance issues. This study aimed to develop metoprolol-loaded sustained-release microspheres using a Quality by Design approach to provide consistent therapeutic effects over an extended period. The formulation utilized Eudragit RL 100, HPMC, PVP, and ethyl cellulose as polymers, optimized through a custom design in JMP® software, which simultaneously screened and optimized formulation parameters. The critical material attributes and critical process parameters included polymer type, drug-to-polymer ratio, solvent, stirring rate, and time. The critical quality attributes were selected as particle size, encapsulation efficiency, drug release profile, and % yield. The formulation trials were prepared and evaluated as per the design matrix of custom design and optimized numerically using the prediction profiler which showed 0.63 on a 0-1 scale. The optimized formulation achieved a controlled drug release, with an initial burst of less than 20% at 1 hour, followed by sustained release, ensuring patient compliance and therapeutic efficacy. Using Eudragit RL 100 resulted in the most favorable outcomes in terms of particle size, encapsulation efficiency, and % yield. The optimized formulation, validated through predictive modeling, promises a robust and efficient solution for hypertension management