Carbapenems are β-lactam antibiotics used against enterobacterial isolates; the effectiveness of them has become seriously controversial. The most common genes encoding Carbapenemase include blaNDM-1 and blaOXA-48, which are transmitted through plasmids such as horizontal gene transfer. This study was conducted to trace these two genes in Enterobacteriaceae strains isolated from clinical samples in the southeast of Iran. A total of 200 Gram negative isolates were collected from hospitals in Zahedan, Iran, over one year. The minimum inhibitory concentration for imipenem and meropenem was assessed by using an Epsilometer (E-Test). The presence of a carbapenemase enzyme was also investigated using the Modified Hodge Test (MHT). The blaOXA-48 and blaNDM-1 genes were detected by PCR. Among the 200 isolates recovered, 60 carbapenem-resistant strains were identified. MHT also turned out positive for 31 of the samples. The blaNDM-1 gene was traced in 25 isolates. The blaOXA-48 gene was present in 20 strains, and blaOXA-48 and blaNDM-1 were simultaneously present in 15 isolates. Given the relatively high frequency of the studied resistant genes in this region of Iran, screening measures are mandatory for preventing the spread of these isolates to other parts of the country.