This chapter presents the application of fractional differential operator in modelling and control of a three-tank interacting level process. In cases where the usage of sensors for the measurement of primary variable, which is the level of third tank in present case, is physically or economically not feasible, the measurement of secondary variable (i.e., second tank level) is used to determine the level of third tank for control purpose, known as inferential control scheme. The process is modeled and linearized around the operating points, resulting in third order plant, which is approximated to lower order integer and non-integer model. Both conventional integer order PI (IO-PI) & PID (IO-PID) and fractional order PI (FO-PI) & (FO-PID) controllers are implemented for this inferential control. Extensive simulation studies performed using MATLAB validate the supremacy of non-integer order model and controller over integer order model and controller. Genetic algorithm (GA) is being applied for both, firstly for reduced order model approximation and secondly for controller tuning.