Conventional immediate-release medication formulations used to treat OAB frequently call for frequent dosing, which can result in inconsistent plasma drug levels and poor patient compliance. In order to provide longer therapeutic activity and better patient adherence, the current study focuses on developing and evaluating sustained release (SR) matrix tablets containing the β3-adrenergic receptor agonist mirabegron. Hydrophilic polymers including polyethylene oxide (PEO) and hydroxypropyl cellulose (HPC) were used in the formulation of Mirabegron SR matrix tablets utilizing a top-spray granulation technique. By taking into account important factors including polymer concentrations and lubricant levels, the formulation was adjusted using Box-Behnken Design (BBD). To guarantee the powder blend had appropriate flow characteristics, pre-compression parameters such bulk density, tapped density, Carr's index, Hausner's ratio, and angle of repose were assessed. Hardness, friability, weight fluctuation, and drug content homogeneity were all assessed after compression. To replicate gastrointestinal circumstances, in vitro drug release investigations were conducted in various pH mediums. Following appropriate kinetic models, the improved formulation showed prolonged, regulated, and sustained drug release. DSC, FTIR, and XRD compatibility tests verified that there were no notable drug–excipient interactions, demonstrating the formulation's stability. The findings showed that polymer concentration is a key factor in regulating drug release behavior. Therefore, by increasing therapeutic efficacy, lowering dosage frequency, and boosting patient compliance, the new sustained release matrix tablets of mirabegron present a viable strategy for the efficient control of overactive bladder.