In the Indus River Basin, groundwater plays a key role in mitigating the water storage fluctuations due to climate variation and meeting the rapidly increasing water demand in agriculture dominated basins. A comprehensive understanding of groundwater dynamics is essential for a transition to more efficient and sustainable water resources management. To gain detailed insight response of water flows and storage in the Indus aquifers to agricultural activities, we build a high resolution 3D regional groundwater flow model for the entire basin. However, in practice, regional flow models, as they are most widely used, suffer from calibration challenges. To address the sparsity of in-situ groundwater data in the region and to acquire a realistic reproduction of flow dynamics, we calibrate the model using both in-situ and satellite-based estimates of ground states. We test the advantage of such a multi-objective approach by comparing its results with a single-objective approach in which we constraint the model parameter only against in-situ data. We examine and discuss the model results for flow and storage conditions, which reveal: 1) depth to water table has decreased (1998-2007) almost exclusively in urban areas (1 m), and 2) groundwater storage depletion averaged ~5cm in equivalent water thickness basin-wide over 20 years of simulations. Groundwater storage depletion results primarily from intensive groundwater withdrawal to meet extensive irrigation demands. Optimizing crop patterns and associated groundwater extraction in space and time could improve groundwater conditions.