Immune checkpoint inhibitors such as pembrolizumab have revolutionized cancer treatment but can trigger severe cutaneous immune-related adverse events, including autoimmune bullous disorders. Most reported cases of pembrolizumab-associated bullous pemphigoid involve hemodynamically stable patients suitable for confirmatory skin biopsy with direct immunofluorescence. However, data are limited regarding critically ill, neutropenic patients where invasive diagnostic procedures and aggressive immunosuppression pose substantial risks. We report a 72-year-old woman with stage IIIB triple-negative breast cancer receiving neoadjuvant carboplatin, paclitaxel, and pembrolizumab who presented with febrile neutropenia and septic shock. She rapidly developed widespread bullae and erosions on both pressure-bearing and non-pressure-bearing sites. Given profound neutropenia and hemodynamic instability requiring vasopressor support, skin biopsy was deferred. Clinical diagnosis of pembrolizumab-induced autoimmune bullous eruption was based on temporal association with drug exposure, characteristic morphology, and distribution beyond typical pressure points. Pembrolizumab was discontinued, and empiric high-dose intravenous corticosteroids were initiated, but the cutaneous eruption progressively worsened. The patient developed refractory septic shock and died on hospital day 6. This case illustrates the profound diagnostic and therapeutic challenges of managing suspected immune checkpoint inhibitor-induced bullous disease in critically ill, neutropenic patients, where clinicians must balance the risks of invasive diagnostics and further immunosuppression against the morbidity of untreated immune-related adverse events. Heightened clinical suspicion and multidisciplinary collaboration are essential in such complex scenarios.