The coast of Chile and the spatial clustering of shellfish aquaculture facilities in the north-central coast and inside inlets within the southern fjord sector, provide a unique natural laboratory to study the effect of multiple environmental drivers (MED’s) and global market drivers on the aquaculture socio-ecological system. The coast is characterized by spatial-environmental heterogeneity in oceanographic conditions and ecological patterns. Coastal upwelling areas, such as those found in northern-central Humboldt Current System off Chile, are predicted to be strongly affected by OW, OA and DO. Coastal upwelling waters have low dissolved O2 and are CO2 supersaturated resulting in lower ocean pH. Local to mesoscale upwelling events also expose the coastal biota to low O2 waters. Interestingly, global warming is projected to intensify the South Pacific Anticyclone, maintaining cooler temperatures off the coast of Chile through increased land-ocean temperature contrast. In brief, a cool, acid, and breathless coastal ocean can be expected in the near future for the north-central coast. In contrast, in southern Chile (e.g. Chiloé), non-seasonal freshwater discharges flow into channels and fjords. Riverine waters are acidic in comparison with oceanic waters, due to its low alkalinity, and high dissolved inorganic carbon and pCO2. Thus, MED’s potentially will impact the growth and survival of economically valuable shellfish. The coastal waters also receive large amounts of pollutants (e.g. drugs, nutrients, metals, etc). Local sources range from mining and industrial activities in the north, nutrients and pollutants associated to domestic sewage and agricultural runoff in the center, and salmon farming residues and siltation from forestry in the south. A new, science-based understanding of the interactions among complex drivers will be of particular relevance for the economic analysis of vulnerabilities for the aquaculture sector under future global change scenarios, and in the development of conservation and management strategies for the public sector. The Chilean economy is dependent on a growing aquaculture sector. MED’s will challenge current biological and socio-economic adaptive capacity with the risk of crossing critical thresholds with uncertain repercussions for the industry. Chile provides a unique opportunity for MUSELS to build the basic understanding on multiple environmental and socio-economic drivers aimed at developing an adaptive capacity in the shellfish socio-ecological system through a science-based approach.