The case discussed involves a 41-year-old Italian man who was a candidate for chimeric antigen receptor T-cell therapy (CAR-T) for mediastinal diffuse large B-cell lymphoma. His CAR-T treatment was postponed several times due to prolonged relapsing COVID-19 and new onset of pulmonary Mycobacterium tuberculosis diseases. After 11 weeks of antimycobacterial treatment, CAR T-cell therapy was performed, but complicated by cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Two months after CAR-T, the patient developed invasive pulmonary aspergillosis due to A. fumigatus. He was successfully treated with a 6-month course of antitubercular therapy and an 8-month course of antifungal therapy with isavuconazole. Lobectomy was performed due to episodes of severe hemoptysis. The challenging issues of diagnosis, choice, and management of treatments, including drug-drug interactions and length of therapy, are discussed.