This study synthesizes results from observations, laboratory experiments and models to showcase how the integration of scientific methods and indigenous knowledge can improve our understanding of (a) past and projected changes in environmental conditions and marine species; (b) their effects on social and ecological systems in the respective communities; and (c) support management and planning tools for climate change adaptation and mitigation. The study links climate-ecosystem-economic (CEE) models and discusses uncertainties within those tools. The example focuses on the key forage species in the Inuvialuit Settlement Region (Western Canadian Arctic), i.e., Arctic cod (Boreogadus saida). Arctic cod can be trophically linked to sea-ice algae and pelagic primary producers and are key vectors for energy transfers from plankton to higher trophic levels (e.g., ringed seals, beluga), which are harvested by Inuit peoples. Fundamental changes in ice and ocean conditions in the region affect the marine ecosystem and fish habitat. Model simulations suggest increasing trends in oceanic phytoplankton and sea-ice algae with high interannual variability. The latter might be linked to interannual variations in Arctic cod abundance and mask trends in observations. CEE simulations incorporating physiological temperature limits data for the distribution of Arctic cod, result in an estimated 17% decrease in Arctic cod populations by the end of the century (high emission scenario), but suggest increases in abundance for other Arctic and sub-Arctic species. The Arctic cod decrease is largely caused by increased temperatures and constraints in northward migration, and could directly impact key subsistence species. Responses to acidification are still highly uncertain, but sensitivity simulations suggests an additional 1% decrease in Arctic cod populations due to pH impacts on growth and survival. Uncertainties remain with respect to detailed future changes, but general results are likely correct and in line with results from other approaches. To reduce uncertainties, higher resolution models with improved parameterizations and better understanding of the species’ physiological limits are required. Arctic communities should be directly involved, receive tools and training to conduct local, unified research and food chain monitoring while decisions regarding commercial fisheries will need to be precautionary and adaptive in light of the existing uncertainties.