Radiant floor cooling (FC) systems show strong potential in large modern buildings and are typically combined with mechanical ventilation (MV) to provide fresh air and remove humidity. However, this combination often leads to large vertical air temperature differences, causing local discomfort. This paper analyzes vertical temperature distribution in simulated office and residential rooms with FC + MV using a validated numerical model with a revised wall Prandtl number. Results showed that vertical temperature difference was sensitive to supply air and floor surface temperatures, with floor temperature having a greater impact. The influence of indoor heat sources and envelope loads was minor. Finally, The two-node model was obtained by using the fitting formulas of the vertical air temperature and the absolute errors of internal wall surface temperature and indoor air temperature were within 0.4–1 °C.The research findings may provide guidance for the optimal design and prediction of a hybrid system with a floor cooling system and a mixing ventilation system, and minimize the issue of excessive vertical temperature differences.