The present study was performed to optimize the formulation of metoprolol succinate (MS) sustained release tablets using hydroxypropyl methylcellulose (HPMC) and sodium alginate (SA) as the matrix combination. After investigating the effects of various parameters on drug release, a 2-factor, 5-level central composite design was employed, using the amount of HPMC K4M (A) and SA (318 cP) (B) as the independent variables and the drug percentage released at 1h, 4h, 8h, 20h (Q1, Q4, Q8, Q20) as the responses. Response surfaces were established to obtain the matrix ranges and the main factors affecting four responses. In order to validate the optimization study, six confirmatory runs were performed; indicating high predictability of response surface methodology for MS sustained release tablets. Data fitting to Peppas equation indicated that the mechanism of drug release could be diffusion along with erosion. This matrix combination can be used as a good alternative to the commercially pellet technology, which was complicated, time-consuming and energy-intensive.