Antimicrobial resistance (AMR) has emerged as a formidable public health challenge globally, significantly threatening human health. The COVID-19 pandemic has further intensified the severity of AMR, particularly highlighting the daunting task of managing infections caused by multidrugresistant gram-negative bacteria—a critical issue for frontline healthcare workers. Responding to these growing concerns, the World Health Organization (WHO) revised its bacterial priority pathogens list in 2024 to better strategize against AMR threats. In a parallel effort, the Infectious Diseases Society of America (IDSA) updated its treatment guidelines for tackling antimicrobialresistant gram-negative infections the same year. This article delves into the treatment and care strategies for these pathogens, provides a concise overview of the role of β-lactamases in fostering resistance among Gram-negative bacteria, introduces the updated WHO Bacterial Priority Pathogens List and the IDSA’s latest recommendations on treatment practices. Additionally, it offers insights into effective prevention and management tactics to combat these persistent threats.