The correct inference of gene regulatory network plays a critical role in understanding biological regulation in cells and genome based therapeutics. DNA microarray is the most widely used technology for extracting the relationships between thousands of genes simultaneously. Since S-system is based on the rate law, it is considered as a suitable mathematical model for representing complex biological reactions between genes. As, this problem has multiple solutions, optimized solution need to be identified via different nature inspired metaheuristic algorithms. So, in this paper, a new method is elaborated that helps to infer gene regulatory network for Lung Adenocarcinoma using S-system and Firefly Optimization which is an efficient but simple metaheuristic inspired by natural motion of fireflies. By optimizing the values of parameters of the S-system model, gene network can be easily reconstructed and inferred. Though direct biological validation of the network is not possible, but accuracy of the proposed method can be described as how well the network fit with the initial training data for different genes which is quite satisfactory for our research work. © 2015 IEEE.