Arsenic contamination in sludge and sediment has emerged as a pressing environmental issue with far-reaching implications. This review delves into the multifaceted problem of arsenic contamination, focusing on its complex interactions with microbial resistance genes (MRGs). It explores the key role of microorganisms in the biogeochemical cycling of arsenic, including processes such as reduction, oxidation, methylation, and volatilization. It describes how microorganisms resist arsenic through resistance genes that encode proteins such as efflux pumps, enzymatic detoxification, and intracellular sequestration. Arsenic, a naturally occurring element, can enter sludge and sediment through various natural and anthropogenic pathways, leading to detrimental effects on environmental quality. Understanding the role of microorganisms in arsenic mobilization, transformation, and their ability to resist arsenic toxicity through MRGs is essential for effective mitigation and remediation strategies. This review discusses the sources and distribution of arsenic in sludge and sediment, the intricate mechanisms of microbial arsenic resistance, and the potential implications for environmental management and human health. It also examines current research trends and identifies areas requiring further investigation. By unraveling the interplay between arsenic contamination, microorganisms, and MRGs, this review aims to contribute to a deeper understanding of the issue and guide future research and environmental protection efforts.