The convergence of antibiotic contamination, antimicrobial resistance (AMR), and climate dynamics poses a critical environmental and public health challenge. Freshwater ecosystems are increasingly threatened by the persistent presence of antibiotics, which, coupled with rising global temperatures, accelerate the development and spread of AMR. This review examines the sources, pathways, and mechanisms through which antibiotics enter freshwater systems and how climate change exacerbates these processes. This review discusses this convergence’s ecological and human health impacts, highlighting the implications for biodiversity and public health. It also explored the current monitoring and mitigation strategies, including advanced oxidation processes, natural-based solutions, and policy interventions. Finally, this review identifies critical research gaps and proposes future directions for managing the intertwined threats of antibiotic contamination, resistance, and climate change. It emphasizes the need for integrated, multidisciplinary approaches to protect freshwater resources in an increasingly volatile global environment.