Proteomics has revealed complex immune responses in fruits, leading to the identification of potential disease biomarkers and resistance mechanisms. Fruit diseases caused by fungal and bacterial pathogens present critical challenges to global food security by reducing fruit shelf life and quality. This review explores the molecular dynamics of fruit-pathogen interactions using advanced proteomic techniques. These approaches include mass spectrometry-based identification, gel-based, and gel-free strategies, tailored to the unique compositions of fruit tissues for accurate protein extraction and identification. Proteomic studies reveal pathogen-induced changes in fruit proteomes, including the upregulation of defence-related proteins and suppression of metabolic pathways crucial for pathogen survival. Case studies on tomatoes, apples, and bananas highlight specific pathogen-responsive proteins, such as PR proteins and enzymes involved in ROS scavenging, which play roles in disease resistance mechanisms. The review further demonstrates the utility of proteomic data in identifying early disease biomarkers, guiding genetic improvements for disease resistance, and optimizing pathogen control measures. Integrating proteomic insights with transcriptomics and metabolomics provides a multidimensional understanding of fruit-pathogen interactions, paving the way for innovative solutions in agriculture. Future research should prioritize multi-omics approaches and field-level validations to translate laboratory findings into practical applications. The advancements discussed underscore the transformative role of proteomics in improving food security and sustainability amid challenges posed by climate change and increasing global food demand.