Industrial Symbiosis (IS) envisages a collaborative approach to resource efficiency, encourag-ing companies to recover, reprocess and reuse waste within the industrial network. Several challenges regarding the effective application of IS continue to limit a broader implementation of this area of Industrial Ecology. The MAESTRI project encompasses an Industrial Symbiosis approach within the scope of sustainable manufacturing for process industries that fosters the sharing of resources (energy, water, residues, etc.) between different processes of a single company or between multiple companies. The Industrial Symbiosis approach is integrated with Efficiency Framework in the so-called MAESTRI Total Efficiency Framework. Efficiency Framework is devoted to the combination of eco-efficiency (via ecoPROSYS) and the efficien-cy assessment (via MSM – Multi-Layer Stream Mapping). In this manuscript the benefit of the combination of the Efficiency Framework as an facilitator to a more effective application of In-dustrial Symbiosis, within or outside the company’s boundaries, is explored.