() is the most common chronic bacterial infection, affecting approximately half of the world's population. is a Class I carcinogen according to the World Health Organization, and the International Agency for Research on Cancer (IARC) has linked it to 90% of stomach cancer cases worldwide. The overall pattern points to a yearly reduction in eradication rates of with the likelihood of success further decreasing after each unsuccessful therapeutic effort. Antimicrobial resistance in is a major public health concern and is a predominant cause attributed to eradication failure. As a result, determining 's antibiotic susceptibility prior to the administration of eradication regimens becomes increasingly critical. Detecting and its antimicrobial resistance has traditionally been accomplished by time-consuming culture and phenotypic drug susceptibility testing. The resistance of to different antibiotics is caused by various molecular mechanisms, and advances in sequencing technology have greatly facilitated the testing of antibiotic susceptibility to . This review will summarize antibiotic resistance patterns, mechanisms, and clinical implications. We will also review the pros and cons of current antibiotic susceptibility testing methods. Along with a comparison of tailored susceptibility-guided regimens and empirical therapy based on the latest evidence, an evidence-based approach to such situations will be explored.