Pulmonary mucormycosis is a severe, often fatal infection caused by fungi of the order Mucorales. Broadly antifungal resistant, mucormycosis often requires surgical intervention in addition to intravenous treatment with the nephrotoxic antifungal amphotericin B. This form of mucormycosis relies upon inhaled fungal cells invading the pulmonary epithelium within the lower airways in a process that is not completely understood. Of all the causative agents of mucormycosis, Cunninghamella bertholletiae is associated with the highest mortality. Despite this, most research on the host-pathogen interactions that mediate mucormycosis focuses on the more common Mucorales pathogen, Rhizopus delemar. In this thesis, I use an omics-guided strategy to identify host factors that promote C. bertholletiae infection in pulmonary epithelium. To screen for potential host targets of C. bertholletiae, both a transcriptomic approach and a binding-based approach are used. Using the host transcriptome, upstream regulator analysis is employed to predict the receptors that are activated during infection. Meanwhile, host proteins that bind C. bertholletiae are identified through affinity purification of host cell lysates with whole fungal cells and subsequent proteomic analysis. As a host receptor identified through both approaches, Ephrin receptor A2 (EphA2) is further investigated to both confirm the omics findings and to determine the role of this receptor in C. bertholletiae infection. Through the use of orthogonal approaches including immunoblotting and immunofluorescence microscopy, C. bertholletiae is shown to bind and activate EphA2 on pulmonary epithelial cells. The role of EphA2 during C. bertholletiae infection is still under investigation, but the EphA2-Cunninhamella interaction may suppress the immune response. This study is not only the first to examine the interface between human pulmonary epithelium and the understudied fungal pathogen C. bertholletiae, but also the first to identify a potential role for EphA2 in mucormycosis. Furthermore, this research can be used as a framework to identify host factors exploited by other poorly understood pathogens.