Global change projections predict significant impacts on the aquaculture sector leading to a substantial interest in the study of species' ecophysiological responses to increased temperature and shifting salinities. Here, we experimentally evaluated shifts on the fatty acid (FA) profiles of the ragworm Hediste diversicolor under global and local ocean change drivers. This polychaete is a suitable extractive organism for integrated multi-trophic aquaculture (IMTA) designs, as it maximizes the use of otherwise wasted nutrients present in particulate organic matter of farm effluents. Ragworms were collected from intertidal mudflats and subjected to an experimental trial of 28 days under control (24 °C), warming (27 °C) and heatwave (30 °C) scenarios combined with salinity variations (20 and 30) in a full factorial design. Individuals were sampled after 14 and 28 days of exposure (D14 and D28 respectively) for FA profile analysis. Interactions between temperature x day and salinity x day modulated ragworms' fatty acid profiles. Overall, an increase in different FA classes, as well as in ∑n-3 UFA, ∑n-6 UFA and essential fatty acids (EFA) was detected over time in polychaetes exposed to salinity 30, contrary to what was observed in salinity 20. This suggests that salinity 30 is an optimal condition for H. diversicolor FA enrichment. At this salinity, fatty acids from n-3 and n-6 families remained stable at 24 °C and 27 °C, with a decrease being detected at 30 °C (after 14 days of exposure), possibly related to changes in the lipid composition of cell membranes to maintain homeostasis. However, after 28 days, no differences were detected, suggesting that polychaetes can acclimate to elevated temperatures when they are in optimal salinity conditions. In contrast, if an extreme warm event (30 °C) is combined with low salinity (20), all FA classes increase at day 14 and HUFA class remain elevated after 28 days, while ∑n-3 UFA, ∑n-6 UFA, ARA, EPA and DHA decrease, suggesting their potential role in osmotic balance and membrane fluidity. Still, if ragworms are grown at low salinity and the increase in temperature is only moderate, ∑n-3 UFA, ∑n-6 UFA, ARA, EPA and DHA increase. This study shows that heatwaves can have an impact on H. diversicolor aquaculture, especially under low salinity conditions, by decreasing EFA. Risk assessment and adaptation strategies need to be implemented into aquaculture practices to mitigate the impacts of global change on the nutritional profile of farmed species and their overall commercial value.