Antimicrobial resistance (AMR) poses a significant global threat, compromising the effectiveness of antibiotics and leading to increased morbidity, mortality, and healthcare costs. This review examines the epidemiology, mechanisms, and challenges of AMR while highlighting strategic solutions. AMR emerges through bacterial mutations, horizontal gene transfer, and selection pressure caused by inappropriate antimicrobial use in medicine and agriculture. It affects millions annually, with projections of 10 million deaths by 2050 if unaddressed. Key challenges include over prescription, lack of new antibiotics, weak surveillance, and insufficient infection control. Solutions emphasize antimicrobial stewardship, enhanced surveillance, research into novel therapies, public awareness, and global collaboration under the "One Health" approach. Natural products are highlighted as promising alternatives for combating resistant pathogens. Coordinated efforts across governments, healthcare providers, and communities are essential to mitigate AMR and ensure effective treatment of infectious diseases. This article provides a comprehensive framework for addressing AMR through sustainable and collaborative interventions.