Disclosed is a method and system for real-time monitoring and control to optimize operation of a data center by controlling operational parameter of cooling units impacting heat generating devices in the data center. A first-set of temperatures for the heat generating devices obtained continuously for being analyzed. Upon analyzing, the heat generating devices is identified in one of a hot condition and cold condition, and further the data center is categorized in one of hot detection mode and cold detection mode. From the cooling units, a target cooling unit is determined for being operated to optimize operation of the data center. Further, a control signal is iteratively generated comprising gradual changes in the operational parameters for the identified, target cooling unit. The operational parameter further comprises a set-point of the target cooling unit which is incremented or decremented by a predefined value based on the categorization of the data center.