South China has a climate characteristic of high temperature and high humidity, and the temperature and relative humidity inside a Venlo greenhouse are higher than those in the atmosphere. This paper studied the effect of ventilation conditions on the spatial and temporal distribution of temperature and relative humidity in a Venlo greenhouse. Two ventilation conditions, with and without a fan-pad system, were studied. A GA + BP neural network was applied to predict the temperature and relative humidity in fan-pad ventilation in the greenhouse. The results show that the temperature in the Venlo greenhouse ranged from 15.8 °C to 48.5 °C, and the relative humidity ranged from 24.9% to 100% during the tomato-planting cycle. The percentage of days when the temperature exceeded 35 °C was 67.3%, and the percentage of days when the average relative humidity exceeded 70% was 83.7%. The maximum temperature differences between the three heights under NV (Natural Ventilation) and FPV (Fan-pad Ventilation) conditions were 3.4 °C and 4.5 °C, respectively. The maximum relative humidity differences between the three heights under NV and FPV conditions were 8.4% and 21.7%, respectively. The maximum temperature difference in the longitudinal section under the FPV conditions was 3.2 °C, while the relative humidity was 11.4%. The cooling efficiency of the fan-pad system ranged from 16.6% to 70.2%. The non-uniform coefficients of the temperature under the FPV conditions were higher than those under the NV conditions, while the nonuniform coefficients of the relative humidity were the highest during the day. The R2, MAE, MAPE and RMSE of the temperature-testing model were 0.91, 0.94, 0.11, and 1.33, respectively, while those of relative humidity model were 0.93, 2.83, 0.10, and 3.86, respectively. The results provide a reference for the design and management of Venlo greenhouses in South China.