We applied the individual-based, multi-species OSMOSE modeling approach to the West Florida Shelf, with the intent to inform ecosystem-based management (EBM) in this region. Our model, referred to as 'OSMOSE-WFS', explicitly considers both pelagic-demersal and benthic high trophic level (HTL) groups of fish and invertebrate species, and is forced by the biomass of low trophic level groups of species (plankton and benthos). We present a steady-state version of the OSMOSE-WFS model describing trophic interactions in the West Florida Shelf in the 2000s. OSMOSE-WFS was calibrated using a recently developed evolutionary algorithm that allowed simulated biomasses of HTL groups to match observed biomasses over the period 2005-2009. The validity of OSMOSE-WFS was then evaluated by comparing simulated diets to observed ones, and the simulated trophic levels to those in an Ecopath model of the West Florida Shelf (WFS Reef fish Ecopath). Finally, OSMOSE-WFS was used to explore the trophic structure of the West Florida Shelf in the 2000s and estimate size-specific natural mortality rates for a socio-economically important species, gag grouper (Mycteroperca microlepis). OSMOSE-WFS outputs were in full agreement with observations as to the body size and ecological niche of prey of the different HTL groups, and to a lesser extent in agreement with the observed species composition of the diet of HTL groups. OSMOSE-WFS and WFS Reef fish Ecopath concurred on the magnitude of the instantaneous natural mortality of the different life stages of gag grouper over the period 2005-2009, but not always on the main causes of natural mortality. The model evaluations conducted here provides a strong basis for ongoing work exploring fishing and environmental scenarios so as to inform EBM. From simple size-based predation rules, we were indeed able to capture the complexity of trophic interactions in the West Florida Shelf, and to identify the predators, prey and competitors of socio-economically important species as well as pivotal prey species of the ecosystem.