Background: Esophagectomy is associated with substantial postoperative morbidity, with infectious complications remaining a leading cause of mortality. Septic shock represents the most severe infectious complication; however, data on its perioperative predictors and long-term impact after esophagectomy are limited. Methods: We conducted a retrospective observational study including consecutive adult patients who underwent esophagectomy with curative intent for esophageal cancer between January 2015 and December 2024 at a tertiary referral center. Postoperative septic shock was defined according to Sepsis-3 criteria. Demographic, clinical, surgical, laboratory, and oncological variables were analyzed. Independent risk factors for septic shock were identified using multivariate logistic regression. Overall survival was assessed using Kaplan–Meier analysis. Results: Among 106 patients, 19 (17.9%) developed postoperative septic shock. These patients had a lower body mass index, reduced preoperative and postoperative albumin levels, and a higher incidence of advanced lymph node involvement. Septic shock was strongly associated with severe postoperative complications, including anastomotic leakage, hemorrhagic shock, acute respiratory distress syndrome, acute kidney failure, and increased rates of PICU readmission. In multivariate analysis, lower albumin levels at PICU admission (OR 0.54; 95% CI 0.29–0.99) and advanced nodal stage (OR 4.98; 95% CI 1.36–18.3) were independently associated with the development of septic shock. Patients who developed septic shock had significantly higher in-hospital mortality (31.6% vs. 1.1%, p < 0.001) and markedly reduced long-term survival, even among those discharged alive. Conclusions: Postoperative septic shock after esophagectomy is a devastating complication with a profound negative impact on both short- and long-term survival. Hypoalbuminemia and advanced lymph node involvement are independent predictors of septic shock. These findings underscore the importance of multidisciplinary perioperative optimization strategies, including nutritional assessment and tailored surgical planning, to mitigate the incidence and consequences of this life-threatening complication.