<p>Carbapenem resistance, especially among members of the <i>Enterobacterales</i> order, poses a serious challenge to public health today. This scenario is further intensified by the dissemination of plasmids carrying carbapenemase-encoding genes, which complicates the control of multidrug-resistant organisms. In this study, we analyzed plasmid sequences and metadata available in the PLSDB database to investigate the global dissemination of carbapenem resistance genes, examining the taxonomy of the isolates, the source of isolation, and the geographic location. We aimed to identify statistically significant associations between plasmid replicons and carbapenemase genes to better elucidate the patterns of gene dissemination. Significant correlations were observed between the IncL, ColKP3, IncM2, IncC, IncFII(pHN7A8), IncR and IncFII replicons and the <i>bla</i>_OXA−48, <i>bla</i>_OXA−181, <i>bla</i>_IMP−1, <i>bla</i>_NDM−4, ​<i>​bla</i>_KPC−2, <i>bla</i>_KPC−2 and <i>bla</i>_NDM−5 genes, respectively. Interestingly, we identified a negative association between the <i>bla</i>_KPC−2 gene and the IncL and IncX3 replicons, suggesting a possible exclusion or incompatibility mechanism that remains to be elucidated. These findings underscore the complexity of replicon-gene interactions, whose understanding is crucial for the development of more precise and effective interventions, while also highlighting the role of plasmid replicons in shaping the global epidemiology of carbapenem resistance. Additional experimental studies are needed to accurately validate these associations and unravel the molecular mechanisms underlying these findings.</p> Graphical Abstract <p></p>