Purpose of the Review: Climate change is intensifying the pressures on aquatic ecosystems by altering the dynamics of contaminants, with cascading effects on ecological and human health. This review synthesizes recent evidence on how rising temperatures, altered precipitation patterns, and extreme weather events influence chemical and microbial contaminant dynamics in aquatic environments. Recent Findings: Key findings reveal that elevated temperatures enhance phosphorus pollution and algal blooms, increase heavy metal release from sediments, and promote the mobilization of organic pollutants. Concurrently, climate change exacerbates microbial contamination by facilitating the spread of waterborne microbial contaminants, especially posing more pressure to antimicrobial resistance-related contaminants through temperature-driven horizontal gene transfer and extreme precipitation events. Complex interactions between chemical and microbial contaminants like heavy metals co-selecting for antibiotic resistance further amplify risks. The compounded effects of climate change and contaminants threaten water quality, ecosystem resilience, and public health, particularly through increased toxicant exposure via seafood and waterborne disease outbreaks. Despite growing recognition of these interactions, critical gaps remain in understanding their synergistic mechanisms, especially in data-scarce regions. Summary: This review highlights the urgent need for integrated monitoring, predictive modeling, and adaptive policies under a One Health framework to mitigate the multifaceted impacts of climate-driven contamination. Future research should prioritize real-world assessments of temperature effects, urban overflow dynamics during extreme weather, and the socio-behavioral dimensions of contaminant spread to inform effective mitigation strategies.