The energy consumption for cooling electronic equipment in data centers using central systems is significant and will continue to rise. The motivation of the present study research is based on the need to determine optimization strategies to improve and optimize the thermal efficiency of data centers using a simulation-based approach. Here, simulation is used to model and optimize a proposed research data center for use as an environment to test equipment and investigate best practices and strategies such as containment and hybrid cooling. The optimization technique used in this study finds the optimal operating conditions and containment strategies of the data center while still meeting certain thermal conformance constraints. More specifically, optimum cooling units supply flow rate and supply temperature setpoint are sought under different containment configurations including both hot aisle and cold aisle containment strategies in both full and partial setups. The optimization process developed in the present study can serve as a generalized procedure for the optimization of any new air-cooled data center.