The Mekong is one of the largest river in the world. It plays a vital role in the socio-economic development of Southeast Asian countries, where riparian people, plants and animals depend on the river’s annual cycle of flood and drought. However, the river is now facing with several major issues induced by natural conditions and human interventions. The global aim of this study is to investigate the current status of flow and sediment transport in the Lower Mekong River by field survey and modeling approaches. First, we investigated the sediment properties along the river from the fluvial and lacustrine environments to the estuaries. Second, we simulated the inundation and subsequent drying processes of the Tonle Sap lake, an integral part of the Mekong River, located in the Cambodia floodplain, to understand its hydraulic links with the Mekong River. This work was conducted by means of a wetting - drying algorithm implemented in a two-dimensional discontinuous Galerkin finite - element model (SLIM, Second-generation Louvain-la-Neuve Ice-ocean Model, www.slim-ocean.be). Third, based on our first findings of the sediment properties, we reevaluated the impacts of the multi-channel system on alternating the flow and sediment dynamics in the Vietnamese Mekong Delta by applying TELEMAC-2D coupled with SISYPHE module. Thus, sustainable development and operation of this system are essential in such a large scale and complex domain. The research also provides better understanding of hydrodynamic regimes in the region and robust information for the basin authorities to design sustainable management strategies.