A predictive wakeup function for Push-to-Talk-over Cellular (PoC) call setup optimizations in a cellular mobile phone network. In performing the predictive wakeup for call setup optimizations, an originating mobile transmits an event trigger to a real-time exchange that interfaces to a mobile switching center in the cellular mobile phone network. The real-time exchange transmits a wakeup message to one or more terminating mobiles of predicted participants, in order to transition the terminating mobiles of the predicted participants from a dormant state to an active state prior to a call being setup with the terminating mobiles of the predicted participants. The terminating mobiles of the predicted participants are identified by a predictive wakeup mechanism before the originating mobile sends a list of one or more terminating mobiles of actual participants to the real-time exchange. The predicted participants may be determined based on static or dynamic information, including heuristics involving calling patterns.