Wastewater treatment systems have economic and environmental costs associated with their construction and operation. These costs vary with location because of the specific conditions under which a treatment plant must be built and operated. A challenge for authorities is selecting the most appropriate treatment system for a given location. This requires an understanding of how competing systems will perform in a given scenario, and how variations in performance influence the associated costs. Small agglomerations in particular face unique challenges during system selection. These are often rural communities where access to resources and wastewater treatment expertise may be minimal, or come at a higher cost. It is, therefore, evident that appropriate system assessment tools are required to assist in the selection process. The objective of this study was to present a methodology to assess system performance under changing conditions, and elucidate the trade–offs that can occur between capital and operational costs, environmental impact categories, and ultimately between the overall economic and environmental costs. A review of the literature has determined that the life cycle approach provides a holistic understanding of the actual cost of system implementation. Thus, life cycle costing and life cycle assessment were the analytical frameworks selected for the study. A decision support tool that integrated both frameworks was developed to facilitate system analysis in user-defined, site-specific scenarios. Life cycle inventories were compiled with data collected from a selection of wastewater treatment plants, and from life cycle assessment process datasets. The life cycle cost data were compiled from a variety of academic and industry sources. To assess the methodology, ten wastewater treatment systems were evaluated under a range of predetermined site-specific scenarios that varied in scale, loading, discharge limits, and method of sludge disposal. In general, system analyses showed that treatment systems with the capacity to mitigate energy and chemical consumption exhibited more favourable economic and environmental life cycle profiles. The methodology illustrated the importance of conducting system assessment from a life cycle perspective and highlighted system processes and components that provide the greatest potential for system improvement and cost savings.