Background Still, in developing the children are being treated empirically and irrationally with accessible antibiotic without susceptibility testing and minimal lethal dose calculations, defying the probable MDR (multi-drug resistance) isolates. This study was undertaken in the febrile children to determine the antimicrobial susceptibility pattern of Salmonella enterica against commonly prescribed antibiotics. Method All isolates were identified by biotyping and serotyping standard protocols then tested against antibiotics by modified Kirby disk-diffusion method. Minimum Inhibitory Concentration (MIC) of isolates were determined by agar dilution method and compared with disk diffusion results and on nalidixic-acid sensitive/resistant strains. Result Among 1815 enteric-fever-suspects, 90(4.9%) isolates of Salmonella enterica [serovar: 62(68.8%) Salmonella Typhi and 28 (31.1%) Salmonella Paratyphi A] were recovered. The incidence of infection was higher among male, age group 5 to 9, and patient from the out-patient department (OPD). On disk-diffusion test most isolates, were sensitive against first-line drugs, cephalosporins, and macrolides. However, against quinolone, a huge percentile i.e. 93.3%, of isolates were resistant [including 58 Typhi and 26 Paratyphi serovar], and nearly 14% against fluoroquinolones. When MIC breakpoint was adjusted 4µg/ml for azithromycin, ≥1 µg/ml for ciprofloxacin, 2µg/ml for ofloxacin, 8µg/ml for nalidixic acid, 1µg/ml for cefixime, higher sensitivity and specificity achieved while screening decreased susceptibility. Among tested antibiotics, low rate of resistant strain observed on MIC of azithromycin. Also, higher resistance against fluoroquinolones observed on NARS strain. Conclusion Higher susceptibility of Salmonella enterica to first-line drugs (the conventional antityphoidal drugs), third-generation cephalosporins, and azithromycin; advocates for its reconsideration in the implicated therapy. However, lower susceptibility against fluoroquinolones among nalidixic-acid resistant Salmonella (NARS) strain negates its empirical use in children. Keywords Enteric fever, Nepal, children, Salmonella enterica