Data-driven models in a combination of optimization algorithms could be beneficial methods for predicting and optimizing in vitro culture processes. This study was aimed at modeling and optimizing a new embryogenesis medium for chrysanthemum. Three individual data-driven models, including multi-layer perceptron (MLP), adaptive neuro-fuzzy inference system (ANFIS), and support vector regression (SVR), were developed for callogenesis rate (CR), embryogenesis rate (ER), and somatic embryo number (SEN). Consequently, the best obtained results were used in the fusion process by a bagging method. For medium reformulation, effects of eight ionic macronutrients on CR, ER, and SEN and effects of four vitamins on SEN were evaluated using data fusion (DF)-non-dominated sorting genetic algorithm-II (NSGA-II) and DF-genetic algorithm (GA), respectively. Results showed that DF models with the highest R-2 had superb performance in comparison with all other individual models. According to DF-NSGAII, the highest ER and SEN can be obtained from the medium containing 14.27 mM NH4+, 38.92 mM NO3-, 22.79 mM K+, 5.08 mM Cl-, 3.34 mM Ca2+, 1.67 mM Mg2+, 2.17 mM SO42-, and 1.44 mM H2PO4-. Based on the DF-GA model, the maximum SEN can be obtained from a medium containing 0.61 mu M thiamine, 5.93 mu M nicotinic acid, 0.25 mu M biotin, and 0.26 mu M riboflavin. The efficiency of the established-optimized medium was experimentally compared to Murashige and Skoog medium (MS) for embryogenesis of five chrysanthemum cultivars, and results indicated the efficiency of optimized medium over MS medium.