The modeling of coupled food-water systems to represent the effect of water supply variability as well as shocks that may emerge from changes in policies, economic drivers, and productivity requires an understanding of dominant uncertainties. These uncertainties cascade into forecasts of impacts of water management policies, such as groundwater pumping restrictions. This paper assesses how parametric, crop price, crop yields, surface water price, and electricity price uncertainties shape hydro-economic model estimates for agricultural production through a diagnostic global sensitivity analysis (GSA).The diagnostic GSA explores how the uncertainties in combination with a candidate groundwater pumping restriction influence three metrics of concern: total economic revenue, total land use and groundwater depth change. The hydro-economic model integrates a Groundwater Response Function (GRF) by integrating an Artificial Neural Network (ANN) into a calibrated Positive Mathematical Programming (PMP) production model for the Wheeler Ridge-Maricopa Water Storage District located in Kern County, California. Our results show that in addition to groundwater pumping restriction, performance metrics of the system are highly sensitive to prices and yields particularly of profitable crops. These sensitivities become salient during dry years when there is a higher reliance on groundwater.