The emergence of Mucorales infections is an urgent global public health threat rapidly disseminating during the current COVID-19 pandemic. Invasive mucormycosis carries significant morbidity and mortality; this is further compounded by the lack of newer effective antifungals on the horizon. Liposomal Amphotericin (L-AMB) is currently considered the cornerstone of antifungals therapy against mucormycosis; However, two decades later (since the introduction of L-AMB), the outcome remains dismal. Furthermore, adverse events related to therapeutic doses of L-AMB are also a hindrance. There is an imperative need for an alternative therapeutic approach to reduce the high mortality. One such approach is to combine the amphotericin with other agents (e.g., caspofungin, posaconazole, isavuconazole, and iron chelators) that can work synergistically or help in reducing the therapeutic doses of L-AMB. This review aims to highlight the various treatment approaches by gathering the clinical evidence from the literature and considering all potential pharmacological combinations that can provide the direction for future studies.