Isavuconazole (ISA) is a triazole antifungal agent that has been approved for the treatment of invasive aspergillosis or mucormycosis in both children and adults. While the pharmacokinetic features of ISA identified during clinical development have not provided a clear need for therapeutic drug monitoring (TDM), emerging evidence suggests that TDM may be warranted in specific clinical scenarios where confirming drug exposure is critical. This article summarizes the populations requiring exposure verification and found subgroups such as paediatric patients, critically ill patients, those on extracorporeal membrane oxygenation (ECMO), renal replacement therapy (RRT), females and patients with high body mass index (BMI) or Sequential Organ Failure Assessment (SOFA) scores appear associated with reduced ISA exposure. Conversely, low BMI, prolonged use, larger dose, liver dysfunction, older age, Asian race, and cotreatment with CYP3A4/5 inhibitors correlate with increased ISA exposure. While the optimal therapeutic range continues to be refined, maintaining trough concentrations between 2.0 mg/L and approximately 5.0 mg/L in these populations is generally supported for these populations to optimize efficacy while minimizing the risk of toxicity.