Enhancing energy use efficiency and reducing energy demand are important issues for industry and academe. Studies on the ventilation, and air conditioning (HVAC) system highlighted the optimization of individual devices, but did not fully consider global optimization. The heating and cooling mechanism of an HVAC system in the present study comprises multiple chillers, chilled water pumps, condenser water pumps, and cooling towers. This study proposes a smart control model of heating, ventilation, and HVAC systems in manufacturing systems to deal with dynamic indoor cooling demands and outdoor temperature changes. A stochastic mixed integer mathematical programming model optimizes the heating and cooling decisions of the HVAC system for energy conservation. This study also investigates a case of the HVAC system in a TFT-LCD manufacturing firm. Experiment results indicate that the proposed model saves up to 3.2% of total energy in the target HVAC system.