Ceftazidime-avibactam (CA) and CA plus aztreonam (ATM) are the preferred treatment options for KPC and MBL carbapenemase-producing Enterobacterales infections (CPEis). All episodes of monomicrobial CPEis in immunosuppressed patients (IPs) admitted from May 2019 to November 2024, who received definitive antibiotic therapy (AT) with CA or CA + ATM for at least 72 h, were prospectively included. Bacteremic episodes (BEs) and non-bacteremic episodes (NBEs) were compared. Logistic regressions adjusted by propensity score were used to identify variables associated with 30-day overall mortality. In total, 82 CPEis were included (38 NBEs and 44 BEs). BEs more frequently occurred in hematological malignancies (52.3% vs. 15.8%, p = 0.0006), while NBEs were more commonly observed in solid organ transplantation (73.7% vs. 34.1%, p = 0.001). K. pneumoniae was the main isolated microorganism; KPC-CPE was the most common resistance mechanism in both groups, followed by MBL-CPE. The 7-day clinical response, 30-day overall and infection-related mortality between NBEs and BEs were 92.1% vs. 88.6%, p = 0.59, 10.5% vs. 27.3%, p = 0.09, and 2.6% vs. 13.6%, p = 0.11. Septic shock, OR 6.5, 95% CI, 1.58–26.72 (p = 0.01), and refractory malignancy, OR 5.6, 95% CI, 1.03–30.14 (p = 0.046), were associated with 30-day mortality, whereas BEs were not, OR 1.5, 95% CI, 0.36–6.2 (p = 0.56). CPEis in both NBE and BE IPs who received definitive AT with CA or CA + ATM correlated with a high rate of 7-day clinical response and low 30-day infection-related mortality. Underlying malignancy and disease severity were associated with 30-day overall mortality. Regional knowledge of bacterial antibiotic resistance enables the implementation of individualized AT to improve patient survival.