Abstract: Objective To retrospectively analyze the correlation among serotypes, antimicrobial resistance phenotypes, and resistance genotypes of Salmonella isolates from diarrheal cases in Baoshan District of Shanghai from 2023 to 2024, and to provide a reference for the prevention and control of Salmonella infections and the rational use of antibiotics in clinical practice. Methods Salmonella isolates collected from diarrhea surveillance in Baoshan District from 2023 to 2024 were serotyped. The antimicrobial resistance phenotypes were determined using the broth microdilution method, and whole-genome sequencing was performed to analyze resistance genes. Results A total of 64 Salmonella isolates belonged to 17 serotypes, with the predominant ones being Salmonella Typhimurium (25.00%) and Salmonella Enteritidis (18.75%). The tested strains exhibited high resistance rates to ampicillin (60.94%), streptomycin (59.38%), and ampicillin/sulbactam (45.31%). All isolates remained susceptible to ceftiofur and ceftazidime/avibactam. Forty different resistance profiles were identified, and 39 isolates (60.94%) were multidrug-resistant. A total of 80 resistance genes belonging to 13 categories were detected, with the most prevalent being bla_TEM-1 (57.81%), aac(6')-Iy (54.69%), and aph(6)-Id (46.88%). No carbapenem or polymyxin resistance genes were found. The types and numbers of resistance genes varied significantly across serotypes. A high concordance was observed between genotype and phenotype for penicillins (positive predictive value 94.59%, Kappa 0.81), cephalosporins (90.91%, 0.46), cephamycins (100.00%, 0.65), macrolides (77.78%, 0.86), tetracyclines (100.00%, 0.93), and chloramphenicol (95.83%, 0.93). Conclusion Salmonella isolates from diarrheal diseases in Baoshan District exhibit serious antimicrobial resistance. Whole-genome sequencing provides valuable support for resistance surveillance, but it still needs to be integrated with phenotypic susceptibility testing for comprehensive assessment. Further studies are warranted to elucidate the mechanisms and transmission patterns of resistance in Salmonella.