The Tagus Estuary is the largest estuarine system in the Iberian Peninsula. Located in a heavily populated metropolitan area (Lisbon), the estuary-coastal continuum is subject to significant natural variability (e.g., tidal variations, winds, river inflow, etc.) and human pressures (e.g., sewage outflow, infrastructures, coastal reclamation, dredging, etc.). Since the 1980s, the estuary has been a natural laboratory for a great number of multidisciplinary studies, but also a numerical laboratory to test models and to develop new ideas and numerical methodologies. Hydrodynamic and biogeochemical models have been used ever since to ascertain the main spatial and temporal features of the Tagus system, connecting its dynamic to its biogeochemical cycles, providing numerical tools used to increase knowledge and to manage the estuary and nearby coastal waters. The main objective of this paper is to present a synopsis of the scientific output related to numerical studies in the Tagus system, by reviewing more than fifty papers published over the past four decades. Our work provides a historical background and description of the numerical models implemented to address estuarine hydrodynamics, nutrient uptake, primary production, light availability, seasonal and annual cycles and the link between physical, biological and chemical estuarine oceanography.