Polyhydroxyalkanoates (PHAs) are thermoplastic polyesters synthesized by Ralstonia eutropha and other bacteria as a form of intracellular carbon and energy storage and are accumulated as lipid inclusions in the cytoplasm of these bacteria. The modeling and optimization of PHA production by fermentation from industrial waste (ice cream residue) was studied by employing statistical experimental design methods. A series of iterative experimental designs was used to find optimal factor conditions (medium components and fermentation process time) in the order of fractional factorial design, path of steepest ascent, and full factorial augmented with axial design (rotational central composite design). An optimal range characterized by lipid (15 mg/mL) and % lipid (88%) values was found and further investigated to verify the optimal conditions for PHA production from ice cream (56.68 mL of ice cream or 56.68% ice cream in water [v/v], 5.03 mL of buffer, 1 mL of mineral salts solution, 100 mu L of trace element solution, 100 mL of seed culture, and 213.76 h of fermentation time).