Background Cryptococcosis is a severe but rare opportunistic fungal infection predominantly affecting immunocompromised individuals, such as posttransplant patients. The diagnosis is frequently delayed due to non-specific symptoms and lower incidence than other fungal infections. Case Report A case of a 50-year-old male renal transplant recipient who developed disseminated cryptococcosis complicated by multi-organ failure is presented. Despite adherence to international treatment guidelines, the patient's condition rapidly deteriorated due to the extensive immunosuppression required for transplant rejection management. The patient developed pneumonia and was diagnosed with disseminated cryptococcosis on the 10th day of hospitalization, with Cryptococcus gattii identified in the pulmonary system and pleura. The patient underwent multiple interventions, including bronchoscopy, lobectomy, and pneumonectomy. Despite aggressive treatment, the infection progressed, leading to severe complications, such as neurological decline, gastrointestinal bleeding, and ultimately, multi-organ failure. The patient passed away after 53 days of hospitalization. Conclusion This report highlights the importance of early diagnosis and multidisciplinary management in post-transplant patients with suspected opportunistic infections. The high mortality associated with disseminated cryptococcosis, particularly in severely immunosuppressed patients, underscores the need for vigilance and prompt intervention to improve patient outcomes.