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One of the crucial public health problems today is emerging and re-emerging of multidrug-resistant bacterial pathogens coupled with a decline in the development of new antimicrobials. Non-typhoidal Salmonella is classified among the multidrug-resistant bacterial pathogens of international concern. To predict their multidrug resistance potentials, 19 assembled genomes (partial genomes) of 23 non-typhoidal Salmonella isolated at the Yaounde abattoir between December 2014 and November 2015 from live cattle (n=1), beef carcass (n=19), butchers’ hands (n=1) and the beef processing environments (n=2) were explored using whole-genome sequencing. Phenotypically, while approximately 22% (n=5) of Salmonella isolates showed moderate resistance to streptomycin, 13.04 % (n=3) were multidrug-resistant. Genotypically, all the Salmonella isolates possessed high multidrug resistance potentials against several classes of antibiotics (third-generation cephalosporin and fluoroquinolone), which are assigned highest priority drugs by the World Health Organization. Moreover, more than 31% of the isolates exhibited resistance potentials to polymyxin, considered as the last resort drug with both clinical and veterinary relevance. Additionally, close to 80% of non-typhoidal Salmonella isolates in this study harboured ‘‘silent resistant genes’’ and thus constituted potential reservoirs of antibiotic resistance to other foodborne bacteria. Plasmids also appear to play a critical role in the horizontal transfer of antibiotic resistance genes of some isolates. The isolates showed a high degree of pathogenicity and possessed key effector proteins to establish infection in their hosts, including humans. The overall results demand prudent use of antibiotics and constant monitoring of antimicrobial resistance of non-typhoidal Salmonella in the Cameroonian abattoirs.Author summaryNon-typhoidal Salmonella has been classified among the multidrug resistant bacterial pathogens of international concern. A growing resistance to a broad range of antibacterial compounds in animals and clinical settings has been reported in Non-Typhoidal Salmonella. Current knowledge of their antibiotic resistance profile is essential to inform policy decisions for the choice of appropriate management of invasive salmonellosis. The significance of our research consists in predicting the multidrug resistance, pathogenicity and virulence potentials of Salmonella organisms using whole genome sequencing. This unveils the need for the development of a diagnostic model that takes into account the genotype–phenotype antibacterial resistance profile of Salmonella, which is of both clinical and veterinary relevance.