In this study, we employed an integrative multi-omics approach—including proteomics, phosphoproteomics, and acetylomics—to systematically investigate the effects of MRSA on protein expression and post-translational modification (PTM) patterns in C. albicans. Our results revealed that the presence of MRSA significantly altered the expression of virulence-associated proteins and reshaped the phosphorylation and acetylation levels of key proteins involved in critical signaling and metabolic pathways. These alterations were primarily linked to biological processes such as energy metabolism, metabolic reprogramming, and stress response. Functional enrichment analyses further suggested that these PTMs may play pivotal roles in regulating C. albicans pathogenicity and environmental adaptability. Additionally, in vitro enzyme activity assays demonstrated that MRSA-induced lysine acetylation modulated the activities of glyceraldehyde-3-phosphate dehydrogenase and homoisocitrate dehydrogenase, implicating this modification in metabolic adaptation and functional reprogramming of C. albicans. In conclusion, this study provides novel insights into the MRSA-mediated regulation of fungal physiology via post-translational modifications, offering a new theoretical basis for understanding fungal pathogenesis and developing improved anti-infective strategies in the context of bacterial–fungal interactions.