Thermodynamic properties and vaporization of the Cs2O-SrO-Al2O3-SiO2 system, which is relevant to the development of functional ceramics and nuclear waste immobilization, were studied using Knudsen effusion mass spectrometry at 640–1200 °C for the first time. Samples of the system were prepared by the solid-state synthesis and characterized using the X-ray fluorescence and diffraction analyses. The principal findings of the study are the Cs and O2 partial vapor pressures, the Cs2O activities, and the Cs2O partial molar enthalpies of vaporization and mixing. Experimental data revealed significant negative deviations from the ideal behavior and were compared with the results of calculations by the semi-empirical Kohler method and the generalized lattice theory of associated solutions, providing insights into the Cs2O-SrO-Al2O3-SiO2 thermodynamics over a wide concentration range. Comparison of the experimental and calculated Cs2O activities in the Cs2O-SrO-Al2O3-SiO2 system at the temperatures 927 °C and 1057 °C led to a conclusion that additive contributions from the corresponding binary systems alone yield only rough estimates of these thermodynamic values in the Cs2O-SrO-Al2O3-SiO2 system.