Carbapenem resistance among Gram-negative bacteria has emerged as a major global public health concern, significantly complicating the management of healthcare-associated and community-acquired infections. This narrative review aims to summarize emerging epidemiological trends, underlying resistance mechanisms, clinical implications, patient outcomes, and recent therapeutic advances related to carbapenem-resistant Gram-negative bacteria. Relevant literature published between January 2000 and October 2026 was considered from databases including PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. The review focused on major resistant pathogens, including Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. Key resistance mechanisms included carbapenemase production, particularly KPC, NDM, and OXA-type enzymes, reduced outer-membrane permeability, and efflux pump activity. The reviewed evidence highlights the association between carbapenem resistance, limited treatment options, delayed effective antimicrobial therapy, prolonged hospitalization, increased healthcare costs, and elevated mortality risk. Newer antimicrobial agents and combination regimens offer additional treatment options; however, their effectiveness may be limited by emerging resistance, variable susceptibility patterns, and restricted availability. The findings emphasize the importance of rapid diagnostic testing, antimicrobial susceptibility-guided treatment, antimicrobial stewardship, infection prevention and control, and coordinated surveillance. Further high-quality multicentre studies are required to clarify regional resistance patterns, evaluate emerging therapeutic strategies, and improve patient outcomes.