Isavuconazole, a triazole-class antifungal, is effective and safe for both primary treatment and salvage therapy in a variety of fungal infections. This article reviews recent knowledge on the role of this antifungal in the treatment of mucormycosis and breakthrough invasive fungal infections (bIFI) during antifungal therapy. Isavuconazole has demonstrated favorable clinical outcomes and a good safety profile in various patient populations with mucormycosis, including those with comorbidities such as diabetes mellitus or severe immunosuppression. Particularly noteworthy is the fact that drug interactions in patients with mucormycosis, where a solid organ transplant was a predisposing factor, have been effectively managed. In the treatment of bIFIs, the use of isavuconazole requires a thoughtful reflection about the fungal species involved and their susceptibility profiles. This is highly dependent on the antifungal agent administered before the onset of bIFI. Early diagnosis and appropriate antifungal therapy are essential to improve outcomes in patients with mucormycosis and bIFIs. Isavuconazole represents a valuable option for managing these complex infections.