Marine ecosystems associated with mid-oceanic elevations harbour unique pelagic and benthic biodiversity and sustain food webs critical for Nature’s contributions to people (NCP). The United Nations Sustainable Development Goals and the Convention on the Law of the Sea recognize the need to implement ecosystem-based management approaches to conserve the structure and functioning of oceanic and deep-sea ecosystems within sustainable reference points. However, uncertainties regarding the interactions between multiple drivers of change, and their impacts on the state of these ecosystems and the NCP, present significant challenges to effective management. Trophic models offer a holistic approach to identify the main drivers affecting the dynamics of marine ecosystems. Here, we used a food web model of the open-ocean and deep-sea environments of the Azores for identifying the drivers that best explain historical biomass trends of demersal fish of high commercial value. Our hindcast simulations suggested that historical trends can be explained by the combined effects of deep-sea fisheries exploitation and variability in environmental conditions, likely dominated by primary productivity anomalies. In particular, deficits in primary production and high levels of fishing exploitation might have contributed to the pronounced decline in biomass observed between 2008 and 2012. These findings reinforce that failure to consider environmental factors in ecosystem-based management may result in shortfalls at achieving biodiversity conservation and sustainability objectives, particularly in the context of climate change.