Due to the impairment of immune function and long-term exposure to high-risk infection environment, patients in the intensive care unit (ICU) have a significantly higher prevalence of multidrug-resistant organism (MDRO) infection than those in other departments, MDRO can prolong hospital stay, decrease antimicrobial efficacy, increase medical cost and mortality, threaten medical quality and patient safety, cause multidimensional economic loss, and affect hospital operational efficiency. The risk factors for MDRO infection include patient-related factors and medical-related factors. The surveillance results of antimicrobial resistance in China in 2024 showed that MDRO in ICU was mainly Gram-negative bacteria, with common bacterial strains having a resistance rate of over 50% to commonly used antimicrobial agents. The detection rate remains high and the resistance spectrum continues to evolve, posing a severe situation for prevention and control. There is an urgent need to establish a multidimensional prevention and control system, including strengthening prevention and control through visual sign management, adenosine triphosphate (ATP) bioluminescence detection, and anhydrous care plans. Meanwhile, case trac-king method and multidisciplinary team collaboration are utilized to enhance efficiency. The core strategy focuses on implementing graded management of antimicrobial agents and developing non-antimicrobial therapy, and based on these, promoting precise prevention and control, standardizing clinical medication, and enhancing public awareness, so as to effectively reduce the risk of MDRO infection. This paper systematically reviews the research progress on risk factors as well as prevention and control strategies for MDRO infection in ICU, and suggests strengthening prevention and control of the heavy economic burden caused by MDRO infection, standardizing antimicrobial use, and enhancing public awareness on infection risks.