In recent decades, efficiency has been the flagship for the achievement ofenvironmental sustainability, but it has been demonstrated that efficiency alone is not capable of guiding technological efforts beyond fine-tuning of old schemes that are intrinsically unsustainable. Therefore, this dissertation explores theuse of systems analysis, in the form of a Multi-sectoral Systems Analysis (MSA),for environmental sustainability assessment supported by a novel set of socio-ecologicalindicators designed using not only eco-efficiency but also eco-effectiveness concepts.For now, the focus of the MSA framework is on flows of materials (water, nitrogen, phosphorus, and carbon), and energy, as they pass through a web of processes described by a total of five industrial sectors: water, forestry, food, energy and waste management. This kind of analysis reveals the advantages of studying different substances simultaneously (N, P, C, water, and energy) in addition to interpreting them individually. The uses of the MSA framework are illustrated by a three-part case studyusing the Upper Chattahoochee Watershed as the system. The first part investigatesmaterial and energy flows with the purpose of gaining insight into the magnitude of theseflows, thereby establishing what it is referred as the emph{base case}. Results show thatnatural flows are predominant in the water and energy cycles. Human manipulations of waterare less than 30% of the amount received as precipitation, while the total energy requirement of the system is 3% of the solar input. On the other hand, the cycle of nutrients (N, P, C) is strongly related to the flows of the poultry industry, fuel consumption, fertilizer use, and biomass use.The second part of the case study elaborates a forward approach for assessing the improvement of the system, as measured by the set of indicators, prompted by the introduction of three technologies: urine separation (UST), pyrolysis of poultry litter (PLP), and pyrolysis ofmunicipal sludge (MSP). This exercise reveals that the selection of technological solutionsmust consider which is the material of interest. Urine separation and municipal sludge pyrolysis were the most advantageous combination for the recovery of nitrogen, but for phosphorus, sludge pyrolysis alone appears to be adequate. The third part of the case study couples the Regionalized Sensitivity Analysis (RSA) procedurewith the MSA framework as an inverse approach to identifying those parameters, and consequently those flows and sectors, that are emph{critical} for attaining targets defined in terms of indicators.The results indicate that to improve the performance of a select set of indicators by 30%, certain aspects of the system, such as runoff from impervious areas, emissions from coal andnatural gas use, fuel consumption for transportation, and poultry litter, are emph{critical}.Additionally, it is shown that there are other sources of nutrients to the sewer network, besides household wastewater, that are also relevant for improving the system.The modeling platform upon which the MSA framework is built makes this a versatile tool that can be used for assessing the impact of infrastructure changes and management decisions. Moreover, in the more general context, this dissertation can be seen as a step forward towardsanswering questions such as how human-managed systems can become a force for good within the environment.