Industrial symbiosis (IS) involves transferring waste materials and/or energy flows between stakeholders to enhance resource efficiency and reduce environmental impacts. The success of these transactions depends on supply–demand matching, technical feasibility of waste integration into industrial processes, economic savings, and compliance with legal and environmental regulations. This paper presents a methodology for the technoeconomic assessment of IS projects, integrating material flow cost accounting (MFCA) and cost–benefit analysis (CBA) incorporating CAPEX and OPEX considerations. MFCA, traditionally used to identify hidden costs from inefficiencies, is adapted here to assess resource utilisation across industry networks. The methodology is applied to two real-world demo cases: a novel fertiliser production process in Escombreras (Spain), where IS focuses on process optimisation and by-product valorisation, and an IS process design in Frövi (Sweden), where CO2 and residual energy flows are exchanged between industrial sectors. The results demonstrate the potential of MFCA-CBA integration to enhance decision making in IS implementation. In Spain, process optimisation led to a 50% reduction in operating costs, whereas, in Sweden, CO2 reutilisation resulted in a 30% increase in resource efficiency. These findings highlight the economic and environmental benefits of IS and provide insights into cost allocation and pricing strategies.