The Gulf of St. Lawrence, a stratified tidal estuary, faces growing concerns regarding the distribution and fate of microplastics. To address and respond to these emerging contaminants, improved understanding of their ultimate fate and transport is required. Validated hydrodynamic models coupled with particle tracking have been proposed as a uniquely valuable tool in this regard; however, important questions remain about the necessity of three-dimensional (3D) models compared to two-dimensional (2D) models, validation methodologies, and the applicability of various modelling tools in these environments. This paper presents a comprehensive study on the development and validation of a high-resolution three-dimensional hydrodynamic numerical model to support predicting the fate and transport of microplastics from urban centres to the Atlantic Ocean through a large, continental-scale domain. By leveraging the TELEMAC-3D solver and a high-resolution modelling grid, the study incorporates complex hydrodynamic processes including salinity stratification and spatially and temporally varying flows and winds. The model's performance was validated against a comprehensive dataset encompassing water levels, velocities, and salinity profiles, demonstrating its high computational efficiency and accuracy in simulating the hydrodynamic conditions necessary for supporting microplastic transport investigations. The findings underscore the importance of using three-dimensional modelling to capture the intricacies of vertical variations in velocities and stratification, crucial for accurately predicting microplastic pathways. This research showcases the potential of TELEMAC-3D as a valuable tool for environmental modelling and management, paving the way for future investigations into the impacts of environmental factors on microplastic dispersion.