Coccidioides posadasii is a pathogenic fungus endemic to the arid regions of the Americas, causing coccidioidomycosis, a debilitating respiratory infection. Coccidioides infection is caused by breathing arthroconidia generated by mycelia that grow in desert soil. Arthroconidia develop inside the lung into massive, multinucleated spherules that are pathognomonic. Despite its significant impact on public health, there remains a paucity of research investigating novel therapeutic approaches to combat this disease. Addressing this research gap, our study employs a multi-faceted approach integrating genomics, proteomics, and computational biology to elucidate the pathogenesis of C posadasii and identify potential therapeutic targets. Our methodology involved retrieving genomic data from 5 strains of C posadasii and generating core proteomes using OrthoFinder, enabling the identification of extracellular proteins as vaccine candidates and metabolic pathways as drug targets. This approach benefits the research study by providing a comprehensive understanding of the molecular mechanisms underlying C posadasii infection, thereby facilitating the development of targeted interventions against valley fever. Our results reveal promising drug-like candidates for drug targets and vaccine targets CID:123631, CID:193962, CID:3045233, CID:6741, CID:214348, CID:11450633 with the identified proteins demonstrating potential efficacy against C posadasii. As we embark on the journey towards translating these discoveries into clinical practice, our findings offer hope for a future where effective treatments for coccidioidomycosis are within reach, promising relief to countless individuals afflicted by this devastating disease.