Aircraft require significant quantities of fuel in order to generate the power required to sustain a flight. Burning this fuel causes the release of polluting particles to the atmosphere and constitutes a direct cost attributed to fuel consumption. The optimization of various aircraft operations in different flight phases such as cruise and descent, as well as terminal area movements, have been identified as a way to reduce fuel requirements, thus reducing pollution. The goal of this chapter is to briefly explain and apply different metaheuristic optimization algorithms to improve the cruise flight phase cost in terms of fuel burn. Another goal is to present an overview of the most popular commercial aircraft models. The algorithms implemented for different optimization strategies are genetic algorithms, the artificial bee colony, and the ant colony algorithm. The fuel burn aircraft model used here is in the form of a Performance Database. A methodology to create this model using a Level D aircraft research flight simulator is briefly explained. Weather plays an important role in flight optimization, and so this work explains a method for incorporating open source weather. The results obtained for the optimization algorithms show that every optimization algorithm was able to reduce the flight consumption, thereby reducing the pollution emissions and contributing to airlines’ profit margins.