Isavuconazole (ISA) is recommended as first-line treatment for pulmonary aspergillosis. In intensive care unit (ICU) patients, ISA shows increased clearance and a larger volume of distribution, but lower plasma concentrations, suggesting the need for dose adjustment. In this case report, a prolonged dosing regimen was applied with the introduction of ISA due to previous failures of standard treatment. This achieved pharmacokinetic steady state with dose optimization guided by serial therapeutic drug monitoring (TDM). The clinical course was favorable without serious adverse reactions. Current evidence for off-label ISA dosing regimens for ICU patients is limited to pharmacokinetic models with no published clinical studies. Due to the limited sample size, further investigation of this clinical scenario is needed for ICU TDM dosing guidelines and strategies.