Systems and methods for a vapor compression system including primary actuators, secondary actuators, primary sensors that provide a primary set of system outputs, and secondary sensors that provide a secondary set of system outputs. A primary controller receives the primary set of system outputs, and produces a primary set of control inputs for the primary actuators, to regulate one or more zone temperatures to set-points and to regulate one or more critical process variables to set-points. A secondary controller receives the secondary set of system outputs, and produces a secondary set of control inputs, to minimize an overall system power consumption. The secondary inputs may include set-points to the primary controller. The primary outputs may include estimates of critical process variables that are used as inputs to the secondary controller.