Diagenetic modeling presents an interesting and robust way to understand sediment–water column processes. Here we present the application of such a model to the Day River in Northern Vietnam, a system that is subject to high levels of domestic wastewater inputs from the Hanoi metropolitan area. Experimental data from three areas of different water and sediment quality, combined with some additional data from the river, are used to set up and calibrate a diagenetic model. The model was used to determine the role of the sediments as a sink for carbon and nutrients and shows that in the dry season, 27% of nitrogen, 25% of carbon, and 38% of phosphorus inputs into the river system are stored in sediments. The corresponding numbers during the rainy season are 15%, 10%, and 20%, respectively. The diagenetic model was then used to test the impact of an improvement in the treatment of Hanoi's municipal wastewater. We show that improved wastewater treatment could reduce by about 17.5% the load of organic matter to the sediment. These results are the first to highlight the importance of sediments as a potential removal mechanism of organic matter and nutrients from the water column in this type of highly impacted tropical urban river, further demonstrating that rivers need to be considered as reaction sites and not just as inert conduits.