The influence of marine aquaculture on benthic biodiversity has attracted considerable scholarly interest driven by the increasing demand for sustainable food production and the urgent need to conserve - and ultimately restore - marine ecosystems. This study presents a comprehensive meta-analysis encompassing 457 case studies drawn from 33 peer-reviewed articles, quantifying the effects of aquaculture operations on benthic biodiversity within the Mediterranean Sea. The evidence-based synthesis indicates that aquaculture exerts a moderate impact on biodiversity relative to undisturbed reference sites. Importantly, our meta-analysis reveals that the magnitude of aquaculture impacts is highly context-dependent, varying markedly across different Mediterranean eco-regions, habitat types and environmental conditions. For example, pronounced effects were detected in the Eastern Basins, whereas Central and Western basins experienced comparatively milder impacts. Additionally, habitat type was a significant determinant, with soft-bottom environments exhibiting more substantial impacts. A subsequent modelling exercise further identified the trophic status of cultured species and water temperature as critical factors; areas characterized by low chlorophyll-a concentrations and elevated temperatures were associated with more severe impacts. These findings have many implications and underscore the necessity for tailored, ecosystem-based and adaptive aquaculture management strategies that incorporate local environmental conditions to promote sustainability. Specifically, our findings emphasise the necessity of: (i) tailoring regulatory frameworks to specific eco-regions based on their vulnerability to aquaculture impacts; (ii) establishing mandatory buffer zones around aquaculture sites - designed according to local environmental conditions and incorporating biodiversity–habitat layers - to protect adjacent ecosystems from direct impacts; (iii) promoting the adoption of integrated multi-trophic culture systems to mitigate the adverse effects associated with single-species farming and to mainstream biodiversity considerations in aquaculture; (iv) enhancing environmental monitoring programs through the development of regionally standardized protocols that include key indicators, such as measures of benthic community biodiversity and functionality (encompassing both macrofauna and megafauna), chlorophyll-a concentrations and water temperature; (v) actively involving stakeholders in the design and implementation of monitoring plans and (vi) instituting adaptive monitoring cycles with periodic revisions, including performance indicators based on biodiversity responses that can be refined over time to inform management actions in the middle of rapidly changing global and local conditions. Future research should prioritize the integration of biodiversity as a critical response variable to advance our understanding and management of the ecological consequences of aquaculture.