The decrease in arable land, water scarcity, and climate change increase the pressure on natural resources and agricultural production systems. In this context, agriculture must ensure food production for the rapidly growing and increasingly urban population of the world. Efforts must be made to obtain the highest yield from the unit area and promote the transition to more sustainable production systems Hydroponics is a modern growing technology mainly applied in greenhouses, which has developed rapidly over the past 30–40 years. Substrate-free hydroponic vertical crops (VC) can reduce the pressure conventional agriculture exerts on resources, saving water and nutrients, and increasing crop yields per unit area. Therefore, this study aimed to validate a proposed predictive model (PM) to simulate water and nutrient uptake in vertical crops under greenhouse conditions. On the basis of the Penman–Monteith equation, the PM estimates transpiration, while nutrient uptake was estimated using the Carmassi–Sonneveld submodel. The PM was experimentally evaluated for vertically grown lettuce under Mediterranean greenhouse conditions during spring 2023. The irrigation technique was a closed-loop fertigation circuit. The experiment consisted of testing two densities (50 and 80 plants·m−2) and three plant positions (low, medium, and upper). ANOVA (p < 0.05) and R2 were used to evaluate the PM performance and crop behavior. The low density and the upper position had significantly higher mass values. The results suggest a high degree of performance for the PM, as the R2 ranged from 0.7 to 0.9 for water and nutrient uptake. Both densities had a yield 17–20 times higher than conventional lettuce production and significant savings in water, about 85–88%. In this sense, the PM has great potential to intelligently manage VC fertigation, saving water and nutrients, which represents an advance toward reaching SDG 6 and SDG 12 within the 2030 Agenda.
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