Systematic and sustainable monitoring approaches capable of tracking the status and trends of keystone characteristics are critical for detecting aquatic ecosystem degradation, identifying the influence of multiple potential stressors, informing environmental protection policy and anticipating future change. At remote lake-rich landscapes, ability to implement and maintain long-term monitoring is often challenged by logistical and financial constraints. At the Peace-Athabasca Delta (PAD; northeastern Alberta, Canada), an internationally recognized remote freshwater landscape threatened by climate change and upstream industrial development (hydroelectric regulation of river flow, oil sands mining and processing), the need for an integrated aquatic ecosystem monitoring program has long been recognized to track changes to the flood regime, water balance, water quality, and contaminant deposition in the abundant shallow lakes. The remoteness and hydrological complexity of the landscape, among other factors, have hindered the implementation of such a program. In recent years, concern over aquatic ecosystem degradation has led to renewed and urgent calls by international and national governance agencies for implementation of a long-term monitoring program. Here, we report on intensive, multi-faceted research performed during 2015-2021 at 60 lakes spanning the delta’s broad hydroecological gradients to develop, evaluate, and apply a framework for integrated assessment of status and trends in water balance, water chemistry and contaminant enrichment. We present the design and approaches used, synthesize the knowledge gained from data collected during the 7-year-long research phase, and provide a foundation for a long-term aquatic ecosystem monitoring program that addresses several recommendations stemming from assessments by UNESCO and key priorities within the Wood Buffalo National Park Action Plan. We suggest the monitoring framework is readily transferable to other remote shallow lake- and pond-rich landscapes threatened by multiple potential stressors.