Industrial symbiosis can well represent a new kind of collaborative network which demands resolute attention to the flow management of materials, by-products, and waste through local and regional economies. Industrial symbiosis engages traditionally separate companies in a collaborative approach to competitive advantage involving physical exchange of different kind of products which are usually disregard by traditional market transitions. The identification of innovative models to support decision-making process in this kind of networks is urgent since it is necessary to close the loop assuring profitability at a single node as well as at system level. This paper proposes the application of the bi-level optimization model as a way to handle this two-stage problem organized into two cooperating layers. As a preliminary result, the model is applied to a simplified case where the nodes can sell their output to the market or share them in the industrial symbiosis to increase the global efficiency.