The ever-increasing global demand for animal products and the need for intensified livestock agricultural operations has resulted in the evolution and development of concentrated animal feeding operations (CAFOs). Although CAFOs have desirable economic benefits, significant environmental and global health impacts have been documented including the development of antimicrobial resistance, production of manure and wastes, and issues related to water management and contamination. The main objective of this study is to synthesize information from published literature regarding the environmental and global health impacts of widespread use of antibiotics, manure management, and water usage and contamination in CAFOs. Additionally, the study aimed to provide recommendations for more sustainable CAFO practices. This systematic literature review involved a 2-staged search process utilizing various databases to identify relevant literature published within the past decade. Included were 8 studies categorized into 3 major themes: antimicrobial resistance, manure management, and water use and contamination. Key findings showed widespread use of antibiotics in CAFOs is correlated with a global increase of antimicrobial resistance; extensive amounts of manure produced from CAFOs contributes to emergence of diseases and GHGs; and significant water usage and wastewater production from CAFOs is unsustainable and creates opportunities for the contamination of water resources, particularly groundwater in many local communities throughout the world. Education of all CAFO stakeholders, public awareness, and sustainable technological solutions are needed to ensure sustainability. Additionally, there is an urgent need to promote and enforce risk-mitigation strategies, unifying national regulations and best practices to minimize environmental public health impacts from CAFOs.