This paper discusses the mathematical modeling and performance optimization of CO2 cooling system of a fertilizer plant using genetic algorithm. The fertilizer plant comprises of various systems viz. shell gasification and carbon recovery, desulphurization, co-shift conversion, decarbonation- CO2 cooling, CO2 removal, nitrogen wash and ammonia synthesis, etc. One of the most important functionaries of a fertilizer plant is CO2 cooling system. The CO2 cooling system of a fertilizer plant has five main subsystems, arranged in series. We propose a mathematical model, which considers exponential distribution for the probable failures and repairs. We also use probabilistic approach and derive differential equations based on Markov birth-death process. These equations are then solved using normalizing conditions to determine the steady state availability of the CO2 cooling system. The performance of each subsystem of CO2 cooling system of a fertilizer plant is also optimized using genetic algorithm. The results of the proposed model of this paper is useful to the plant management for the timely execution of proper maintenance decisions and hence to enhance the system performance.