Industrial Symbiosis (IS) is a systematic and collective (business) approach to optimizing the use of materials and energy among cross-sectoral industries in order to initiate and exhaust extended cascading systems; it is associated with (synergistic) environmental, technical, social, and economic benefits. For monitoring and controlling the development and progress of an IS system, an indicator system must be set up to standardize and assess the IS (sustainability) performance. This study aims to present a quantitative indicator system to enable the tracking of set sustainability targets of an IS system in Industrial Parks (IPs) for goal-directed IS management. The presented guiding framework encourages IP members in IS systems to set sustainability objectives and to evaluate and track their performance over time with a quantitative indicator system. In particular, established and (partly) internationally standardized methods—such as Material Flow Analysis (MFA), Material Flow Cost Accounting (MFCA), Social Network Analysis (SNA), and Life Cycle Assessment (LCA)—are used in order to place the indicator system on a solid and robust foundation and to adequately meet the multi-faceted sustainability perspectives in the form of a combinatorial application for deriving suitable quantitative indicators for all three (environmental, economic, social) dimensions of sustainability. The indicator system, once embedded in an Information Technology (IT)-supported IS tool, contributes crucially to the technology-enabled environment of IS systems, driving sustainability trajectories.