Background: To describe short-term outcomes and independent predictors of 28-dayx mortality in adult patients with hematologic malignancies and septic shock defined by the new Third International Consensus Definitions (Sepsis-3) criteria. Methods: We performed a retrospective cohort study of patients admitted to the medical ICU with septic shock from April 2016 to March 2019. Demographic and clinical features and short-term outcomes were collected. We used descriptive statistics to summarize patient characteristics, logistic regression to identify predictors of 28-day mortality, and Kaplan-Meier plots to assess survival. Results: Among the 459 hematologic patients with septic shock admitted to the ICU, 109 (23.7%) had received hematopoietic stem cell transplant. The median age was 63 years (range, 18–89 years), and 179 (39%) were women. Nonsurvivors had a higher Charlson comorbidity index (P=.007), longer length of stay before ICU admission (P=.01), and greater illness severity at diagnosis and throughout the hospital course (P<.001). The mortality rate at 28 days was 67.8% and increased with increasing sequential organ failure assessment score on admission (odds ratio [OR], 1.11; 95% CI, 1.03–1.20), respiratory failure (OR, 3.12; 95% CI, 1.49–6.51), and maximum lactate level (OR, 1.16; 95% CI, 1.10–1.22). Aminoglycosides administration (OR, 0.42; 95% CI, 0.26–0.69), serum albumin (OR, 0.51; 95% CI, 0.31–0.86), and granulocyte colony-stimulating factor (G-CSF) (OR, 0.40; 95% CI, 0.24–0.65) were associated with lower 28-day mortality. Life support limitations were present in 81.6% of patients at death. At 90 days, 19.4% of the patients were alive. Conclusions: Despite efforts to enhance survival, septic shock in patients with hematologic malignancies is still associated with high mortality rates and poor 90-day survival. These results demonstrate the need for an urgent call to action with higher awareness, including the further evaluation of interventions such as earlier ICU admission, aminoglycosides administration, and G-CSF treatment.