Command information system of systems (CISoS) is the key to acquire operational superiority under SoS operation. A method of effectiveness evaluation for missile combat was proposed based on CISoS. The structure of composing for missile combat oriented CISoS was analyzed, and the mode of collaboration for CISoS was analyzed, too. The effectiveness evaluation frame of missile combat with CISoS and evaluation models were built. The weight of each factor was figured out by AHP. Using an analysis example, the effectiveness and superiority of missile combat with CISoS were expressed. The result shows the rationality and effectiveness of the evaluation frame and modeling.