ABSTRACT Antibiotic resistance in typhoid fever poses a critical public health problem due to the emergence of extensively drug-resistant (XDR) Salmonella, resulting in prolonged illness and treatment failure. Salmonella enterica serovar Typhi is the most predominant among all serotypes and can acquire resistance. The emergence of XDR Salmonella in various regions globally, particularly Pakistan, presents a concerning trend. However, limited data availability impedes a comprehensive understanding of the outbreaks and hinders the development of real-time solutions. Here, we have provided an updated overview of the current outbreaks of XDR Salmonella in epidemic and endemic regions. Treatments of XDR Salmonella infections are challenging, as there are records of treatment failure in humans and animals. However, intensive prevention techniques can be implemented pending the advent of novel antibiotics. Emphasis on antimicrobial stewardship and frequent surveillance of the pathogen should be made to keep track of potential outbreaks in both human and animal populations. Although progress is being made to combat XDR Salmonella within some regions, a unified and efficient effort on an international scale is required to curtail the XDR outbreak before it escalates and leads us back to the pre-antibiotic era.