Resistance to antibiotics has become a significant health crisis in most parts of the world, posing the risk of reducing the usefulness of existing treatment methods and is one of the leading causes of death. Methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae among other multidrug-resistant bacteria have acquired complicated mechanisms, which disempower the standard use of antibiotics. Objective. In this paper, alternate solutions in the form of artificial intelligence, bacteriophage therapy, CRISPR gene editing, developing vaccines, and exploration of natural compounds shall be discussed. Methods. A detailed literature review of peer-reviewed works for the period 2019–2024 was conducted. Resistance-related mechanisms were classified and discussed, such as gene mutations, the production of enzymes, and the efflux pumps. Technological interventions were tested in terms of feasibility, efficacy and potential to use in clinical settings. Results. The use of artificial intelligence in drug design like in the case of halicin showed improvements in speeding up discovery and better targeting the resistant strains. Bacteriophage treatment was specific and its side effect was less. The technology of CRISPR-Cas9 allowed editing the genes precisely to inactivate resistant genes. Probiotics and vaccines boosted immune mechanisms, whereas natural compounds such as curcumin or salinosporamide showed good bacteria killing. Enzyme inhibitor and dual-target antibiotics combination therapy were effective. Conclusion. The fight against antibiotic resistance should be multidisciplinary and multinational because it has to embrace technological innovation, international partnerships and education of the population. They also require long-term research and regulatory framework that should be invested in long-term so that they are safely and clearly implemented. The artificial intelligence combination and molecular biology show a future solution to future resistance.