A mathematical model of Fischer-Tropsch synthesis over an iron-based catalyst was developed for a bench-scale fixed-bed reactor. Parametric sensitivity analysis found that inert fraction, H2/CO ratio, and inlet and wall temperatures are effective manipulated variables. Three optimization strategies, with different combinations of objective functions and manipulated variables, were suggested to optimize conditions using the genetic algorithm, and it was shown by the comparison that maximization of CO conversion and C5+ productivity guaranteed both maximum production by amount of catalyst and sustainable operation by maintaining peak temperatures below an allowable limit, even without including maximum temperature as an objective function.