Food, energy, and water (FEW) nexus studies require reliable estimates of water availability, use, and demand. In this regard, spatially distributed hydrologic models are widely used to estimate not only streamflow (SF) but also different components of the water balance such as evapotranspiration (ET), soil moisture (SM), and groundwater. For such studies, the traditional calibration approach of using SF observations is inadequate. To address this, we use state-of-the-art global remote sensing-based estimates of ET and SM with a multivariate calibration methodology to improve the applicability of a widely used spatially distributed hydrologic model (Noah-MP) for FEW nexus studies. Specifically, we conduct univariate and multivariate calibration experiments in the Mississippi river basin with ET, SM, and SF to understand the trade-offs in accurately simulating ET, SM, and SF simultaneously. Results from univariate calibration with just SF reveal that increased accuracy in SF at the cost of degrading the spatio-temporal accuracy of ET and SM, which is essential for FEW nexus studies. We show that multivariate calibration helps preserve the accuracy of all the components involved in calibration. The study emphasizes the importance of multiple sources of information, especially from satellite remote sensing, for improving FEW nexus studies.Author Contributions: Conceptualization, A.K.; methodology, A.K.; formal analysis, A.K.; investigation, A.K. and M.G.; resources, M.G.; data curation, A.K.; writing-original draft preparation, A.K.; writing-review and editing, A.K. and M.G.; visualization, A.K.; supervision, M.G.; funding acquisition, M.G. All authors have read and agreed to the published version of the manuscript.