The rapid development of multi-Global Navigation Satellite Systems (GNSSs, e.g., BeiDou, Galileo, GLONASS, and GPS) and the International GNSS Service (IGS) Multi-GNSS Experiment (MGEX) brings great opportunities and challenges for real-time determination of tropospheric zenith total delays (ZTDs) and integrated water vapor (IWV) to improve numerical weather prediction, particularly for nowcasting or severe weather event monitoring. In this paper, we develop a multi-GNSS model to fully exploit the potential of observations from all currently available GNSSs for enhancing real-time ZTD/IWV processing. A prototype multi-GNSS real-time ZTD/IWV monitoring system is also designed and realized at the Helmholtz Centre Potsdam GFZ German Research Centre for Geosciences (GFZ) based on the precise point positioning technique. The ZTD and IWV derived from multi-GNSS stations are carefully analyzed and compared with those from collocated Very Long Baseline Interferometry and radiosonde stations. The performance of individual GNSS is assessed, and the significant benefit of multi-GNSS for real-time water vapor retrieval is also evaluated. The statistical results show that accuracy of several millimeters with high reliability is achievable for the multi-GNSS-based real-time ZTD estimates, which corresponds to about 1- to 1.5-mm accuracy for the IWV. The ZTD/IWV with improved accuracy and reliability would be beneficial for atmospheric sounding systems, particularly for time-critical geodetic and meteorological applications.