Artesunate is a poorly soluble drug and liable to aqueous hydrolysis. This study aims to formulate Artesunate as an immediate release tablet through optimization of the melt granulation technique to improve the dissolution of the drug. Three different meltable binders were used (Polyethylene Glycol PEG 6000, Poloxamer 188 and Gelucire 50/13) for granulation step in high shear mixer prior tablets compression step applying Box-Behnken experimental design to determine the significant variables and their interactions that impact dissolution of Artesunate. Optimization mathematical models showed that by increasing binder concentration, D50 was increased, and narrow particle size distribution with minimum fines percentage was produced. Higher binder concentration and impeller speed resulted in retarding tablets dissolution. PEG 6000 and Poloxamer 188 based tablets showed faster disintegration and dissolution than Gelucire 50/13 based tablets, as well as tablets prepared by wet granulation due to hydrophilic pore forming. Melt granulation technique using a low level of PEG 6000 and Poloxamer 188 not only enhanced the dissolution of Artesunate from their immediate release tablets in comparison to traditional wet granulation technique but also maintained the stability of the product under accelerated conditions of heat and moisture.