The water resources that supply most of the megacities in the world are under increased pressure because of land transformation, population growth, rapid urbanization, and climate-change impacts. Dhaka, in Bangladesh, is one of the largest of 22 growing megacities in the world, and it depends on mainly groundwater for all kinds of water needs. The regional groundwater-flow model MODFLOW-2005 was used to simulate the interaction between aquifers and rivers in steady-state and transient conditions during the period 1981–2013, to assess the impact of development and climate change on the regional groundwater resources. Detailed hydro-stratigraphic units are described according to 150 lithology logs, and a three-dimensional model of the upper 400 m of the Greater Dhaka area was constructed. The results explain how the total abstraction (2.9 million m³/d) in the Dhaka megacity, which has caused regional cones of depression, is balanced by recharge and induced river leakage. The simulated outcome shows the general trend of groundwater flow in the sedimentary Holocene aquifers under a variety of hydrogeological conditions, which will assist in the future development of a rational and sustainable management approach.