The VegSyst model, initially developed for nitrogen (N) and irrigation recommendations for greenhouse-grown vegetable crops in southeastern Spain, was calibrated and validated for greenhouse tomato cultivated in soil in Uruguay (South America) for autumn and spring growing seasons. Additionally, the performance of the recalibrated VegSyst model was compared to the calibration for tomato grown in Almeria greenhouses of VegSyst model V3. Five tomato crops, three autumn and two spring crops grown in 2019, 2020 and 2021, were used for model calibration (Spring-19 and Autumn-20) and validation (Autumn-19, Spring-21 and Autumn-21). A major change to the existing VegSyst model (V3) was the incorporation of the Hargreaves-Samani equation adapted to plastic greenhouses to estimate ETo. The recalibrated VegSyst model accurately simulated dry matter production (DMP), ETc, and crop N and K uptake over time for autumn and spring growing seasons. Using the original VegSyst V3 calibration, acceptable results were obtained for DMP and N uptake. A new dilution curve for N content was included. It was derived from pooled data and was described by the power equation %N = 3.4117 x DMP−0.153 (R2 of 0.84). Both, this dilution curve and the critical N curve of VegSyst V3 provided accurate simulation of crop N uptake. Therefore, both can be used in Uruguayan conditions. K uptake simulations were accurate according to the statistical indices used. This was despite that the K dilution curve of %K = 4.359 x DMP−0.005 had a low R2 value. Moreover, simulation with this K dilution curve provided better results than with the dilution curve of VegSyst V3. A decision support system based on the recalibrated VegSyst model will be developed to assist Uruguayan farmers and advisers. It will provide calculation of daily irrigation needs and nutrient concentration tailored to each crop and greenhouse.