A modelling approach applied to the study of ecosystems from a management and conservation point of view allows their complexity to be investigated and represents a tool for meeting sustainability goals, part of the 2030 Agenda for Sustainable Development. Tying into Sustainable Development Goals (SDGs) 13 and 14, the human activities of fisheries and climate change represent two pivotal drivers for the marine environment, acting on keystone predators, such as odontocetes. A calibrated time-dynamic model (Ecopath with Ecosim) was developed to investigate the effects on the odontocetes and their main prey in the Northern Ionian Sea (Central Mediterranean Sea), according to changes in trawl fishery and primary productivity. In particular, the food web of the Gulf of Taranto (GoT) is described by 51 functional groups (FGs), with four odontocetes (striped, common bottlenose, Risso's dolphin and sperm whale) represented as a single FG, and 5 fishing fleets. The calibration of the Ecosim model was carried out during the period 2009–2018 using a combination of automatic and manual fitting procedures. Changes in trawling fishing effort (increases, reductions and bans) and in primary production were tested in the period until to 2040 to detect the effect on the biomass of odontocetes and their main prey. The cumulative effects of the two drivers were assessed using an Interaction Effect Index. Fishery showed negligible effects on all odontocetes, with the exception of the common bottlenose dolphin which respond in a negative way to an increase in fishing effort. The reduction in top-predators due to fishing seems to lead to a reduction in predation pressure on meso‑consumers, and thus to an increase in predation pressure on basal prey. Similarly, the bottom-up effect due to increased primary production tends to be diluted towards the top of the trophic network, with slight effects on odontocetes. The trophic interaction pattern tends to mediate the effects tested in the model with a variety of different outcomes on prey. The application of the interaction effects index could contribute to disentangling the effects of fishing and climate on the food web, providing information to address the analysis required by the SDG 14 targets.