Antimicrobial resistance (AMR) is a growing global health crisis that threatens the efficacy of antibiotics and modern medical interventions. The emergence of multidrug-resistant (MDR) pathogens, exacerbated by the misuse of antibiotics in healthcare and agriculture, underscores the urgent need for innovative solutions. (1) Background: AMR arises from complex interactions between human, animal, and environmental health, further aggravated by the overuse and inadequate regulation of antibiotics. Conventional treatments are increasingly ineffective, necessitating alternative strategies. Emerging approaches, including bacteriophage therapy, antimicrobial peptides (AMPs), nanotechnology, microbial extracellular vesicles (EVs), and CRISPR-based antimicrobials, provide novel mechanisms that complement traditional antibiotics in combating resistant pathogens. (2) Methods: This review critically analyzes advanced antibacterial strategies in conjunction with systemic reforms such as antimicrobial stewardship programs, the One Health framework, and advanced surveillance tools. These methods can enhance resistance detection, guide interventions, and promote sustainable practices. Additionally, economic, logistical, and regulatory challenges impeding their implementation are evaluated. (3) Results: Emerging technologies, such as CRISPR and nanotechnology, exhibit promising potential in targeting resistance mechanisms. However, disparities in resource distribution and regulatory barriers hinder widespread adoption. Public-private partnerships and sustainable agriculture practices are critical to overcoming these obstacles. (4) Conclusions: A holistic and integrated approach is essential for mitigating the impact of AMR. By aligning innovative therapeutic strategies with global health policies, fostering interdisciplinary collaboration, and ensuring equitable resource distribution, we can develop a sustainable response to this 21st-century challenge.
