At present, response surface methodology (RSM) is the most preferred method for fermentation media optimization. However, in the last two decades, artificial intelligence algorithm has become one of the most efficient methods for empirical modelling and optimization. One of the popular developed approaches is Particle Swarm Optimization (PSO), which is used in optimizing a problem. This paper focuses on comparative studies between RSM and PSO in fermentation media optimization for the production of flexirubin production using Chryseobacterium artocarpi CECT 8497T. Two methodologies were compared for in terms of their modeling, sensitivity analysis, and optimization abilities. All experiments were performed accordingly to box-behnken design (BBD), and the generated data was analyzed using RSM and PSO. The sensitivity analysis performed by both methods has given comparative results. Based on the correlation coefficient, the model developed with PSO was found to be superior to the model developed with RSM. The result shows that PSO gives a better pigmentation yield with optimal fermentation concentration