Ecological modelling tools are applied worldwide to support the ecosystem-based approach of marine resources (EAM). In the last decades, numerous applications were attempted in the Mediterranean Sea, mainly using the Ecopath with Ecosim (EwE) tool. These models were used to analyse a variety of complex environmental problems. Many applications analysed the ecosystem impacts of fishing and assessed management options. Other studies dealt with the accumulation of pollution through the food web, the impact of aquaculture or the ecosystem effects of climate change. They contributed to the scientific aspects of an ecosystem-based approach in the region because they integrated human activities within an ecosystem context and evaluated their impact on the marine food web, including environmental factors. These studies also gathered a significant amount of information at an ecosystem level. Thus, in the second part of this review, we used this information to quantify structural and functional traits of Mediterranean marine ecosystems at regional scales as the illustration of further potentialities of EwE for an EAM. Results highlighted differential traits between ecosystem types and a few between basins, which illustrate the environmental heterogeneity of the Mediterranean Sea. Moreover, our analysis evidenced the importance of top predators and small pelagic fish in Mediterranean ecosystems, in addition to the structural role of benthos and plankton organisms. The impact of fishing was high and of a similar intensity in the western, central and eastern regions and showed differences between ecosystem types. The keystone role of species was more prominent in protected environments.