The Merrimack is the only major river in New England that provides domestic water for 600,000 people. It is considered among the most threatened rivers in the U.S. due to historical pollution from centuries of industrial activity, runoff from urban development, discharge of industrial chemicals, and metals contamination. Our work in the Merrimack explores different facets of this pollution problem to determine possible solutions for mitigation. We are measuring the spatio-temporal distribution of plastics along an urban pollution gradient of the Merrimack-Concord watersheds to assess how they correlate with other contaminants and biodiversity, to test whether microplastic biofilm assemblages vary according to environmental conditions and whether these affect pollutant interactions. We are also investigating the distribution and effects of emerging contaminants such as PFAS and pharmaceuticals since the Merrimack-Concord watersheds serve as spawning grounds for diadromous fish that are central to ecosystem functions and commercial /recreational fisheries. Our interdisciplinary research combines field work and experiments with state-of-the-art analytical technologies like molecular sequencing of environmental DNA (eDNA) and metagenomic analysis to advance our understanding of the relationships among emerging contaminants, upstream sources, and biodiversity.