Monitoring product temperature during lyophilization is of critical importance, especially during the process development stage, as the final product may be jeopardized if its process temperature exceeds a threshold value. While conventional thermocouples can track product temperature, they are invasive and can significantly alter the freezing and drying behavior. In this work, a new methodology for non-invasive product temperature monitoring and drying behavior during the entire lyophilization process is proposed and experimentally validated. The method is based on a new flexible wireless multi-point temperature sensing probe that is attached to the outside of the vial. Combining the wirelessly-collected data with advanced multi-physics simulations allows the accurate extraction of the product temperature non-invasively.