Infection with multiple drug resistant (MDR) Escherichia coli poses a life threat to immunocompromised pediatric cancer patients. Our aim is to genotypically characterize the plasmids harbored in MDR E. coli isolates recovered from bacteremic patients of Children's Cancer Hospital in Egypt 57357 (CCHE 57357). In this study, 21 carbapenem-resistant E. coli (CRE) isolates were selected that exhibit Quinolones and Aminoglycosides resistance. Plasmid shotgun sequencing was performed using Illumina nextgeneration sequencing platform. Isolates demonstrated resistant to all beta-lactams, carbapenems, aminoglycosides and quinolones. Of the 32 antimicrobial resistant genes identified that exceeded the analysis cutoff coverage, the highest represented genes were aph(6)-Id, sul2, aph(3″)-Ib, aph(3′)-Ia, sul1, dfrA12, TEM-220, NDM-11. Isolates employed a wide array of resistance mechanisms including antibiotic efflux, antibiotic inactivation, antibiotic target replacements and antibiotic target alteration. Sequenced isolates displayed diverse insertion sequences, including IS26, suggesting dynamic reshuffling of the harbored plasmids. Most isolates carried plasmids originating from other bacterial species suggesting a possible horizontal gene transfer. Only two isolates showed virulence factors with iroA gene cluster which was found in only one of them. Outside the realms of nosocomial infections among patients in hospitals, our results indicate a transfer of resistant genes and plasmids across different organisms. Escherichia coli represents the most frequent sources of blood stream and urinary tract infections worldwide. A continual increase in E. coli antibiotic resistance burdens medical facilities throughout the world by causing difficult to treat infections among patients 1,2. There has been a particular concern regarding the increase in Extended-Spectrum Beta-Lactamase (ESBL)-producing and carbapenem-resistant E. coli. carbapenem-resistant E. coli (CRE) have become resistant to the majority of available antibiotics, including carbapenems which are a last-resort treatment for multidrug-resistant pathogens. This is often accompanied by resistance to fluoroquinolones and aminoglycosides 3,4. The increase in antimicrobial resistance (AMR) frequency presents a global healthcare challenge by limiting the choices of antimicrobials that can be used in the treatment of bacterial infections 5,6. Mobile elements like transposons, integrons and plasmids frequently carry Multiple Drug Resistance (MDR) genetic motifs. These elements can be transferred from foodborne pathogens to human pathogens, increasing their virulence 7. This method has enabled the rapid propagation of AMR among several pathogenic bacterial genera to humans, including E. coli 8. CRE-encoding plasmids are now regarded as the primary vector facilitating this transmission between bacteria 9 .