The primary goals of this cross-sectional study were to screen various food/water, and human samples for the presence of Salmonella species, and to assess the phenotypic and genetic relationship between resistances found in food and human Salmonella isolates to critically important antibiotics. Between November 2019 and May 2021, 501 samples were randomly collected for Salmonella isolation and identification using standard culturing methods, biochemical, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and PCR techniques. Antimicrobial susceptibility testing was performed on confirmed Salmonella species, and PCR was used to investigate the genetic components that confer these resistance traits. Salmonella enterica subspecies enterica was confirmed in 35 (6.99%) of the samples (raw food = 23, ready-to-eat food/drink [REF/D] = 5, human = 7). Seventeen of them were antibioticresistant to at least one class, and eight were multidrug-resistant (MDR) isolates (raw food = 7, human = 1). All Salmonella isolates were susceptible to carbapenems, thirdand fourth-generation cephalosporins and monobactam antibiotics. Resistance phenotypes to aminoglycosides (48.57%), β-lactams (20%) and tetracycline (17.14%), as well as associated genes such as aadA, bla TEM , bla Z and tetA, as well as dfrA and sul1, were prevalent in Salmonella isolates. Colistin resistance genotype (mcr1) was detected in three (8.57%) isolates recovered from egg, cattle mince and rabbit meat, and the total incidence was 14.29% when two isolates exhibited resistance phenotypes were considered. Furthermore, four (11.43%) MDR isolates shared the bla TEM and bla Z genes, and one (2.86%) isolate contained three extended spectrum β-lactams producing genes (ESBL), namely bla CTX , bla TEM and bla Z . The gyrA gene was expressed by one of three foodborne Salmonella isolates (8.57%) with ciprofloxacin resistance phenotypes. To the best of our knowledge, this is the first report from Egypt identifying colistin resistance in Salmonella enterica recovered from cattle minced meat and rabbit meat. Overall, the highest incidence rate of Salmonella enterica was found in cattle-derived products, and it was slightly more prevalent in RTE/D foods than in raw foods. Resistance to critical and clinically important antibiotics, particularly in Salmonella from RTE/D food,