Background: Typhoid fever is a systemic febrile illness that requires prompt antibiotic treatment. Over 21 million people contract typhoid each year mainly due to fecal contaminated food or water and among these 161,000 die globally. Moreover, in southeast Asia including Pakistan, 3.6 cases of typhoid occurred per 100,000 persons/year. Extensively drug-resistant typhoid fever is spreading in Pakistan, raising fears of antibiotic failure at a global level. Methods & Materials: Blood samples (n = 4543) were collected from children suspected of septicemia from a tertiary care hospital in Lahore, Pakistan. Blood samples were collected aseptically in peads BacT/ALERT plus blood culture bottles and placed in BacT/ALERT for up to 5 days. Positive blood culture bottles were sub-cultured on blood and MacConkey agar. Colonies were observed by morphological characteristics. Biochemical confirmation of isolates was carried out by VITEK 2 compact system using GN card. MIC (μg/mL) was determined against 15 different antibiotics using AST-N204 by VITEK 2 compact system. Results: Of 4543 blood cultures samples, 415 (9.1%) were positive for S. Typhi. Among these, 69.1% were MDR S. Typhi while 41.6% were XDR S. Typhi. The highest prevalence of MDR S. Typhi in Peads emergency (167; 40%) followed by peads OPD (90; 21%) and Peads Medical Ward (78; 11.5%). Antibiogram (μg/mL) showed that patients had MDR and XDR S. Typhi was resistant to ampicillin (90%), ciprofloxacin (73%), co-trimoxazole (72.6%) and cefotaxime (67.6%) and ceftriaxone (65.3%) however, 100% sensitive to meropenem and colistin. Conclusion: The present study concluded that the emergence of MDR and XDR S. Typhi in children is a serious public health concern that causes mortality due to treatment failure.