Fruit crops, particularly perennial species, contribute significantly to global nutrition and rural economies but are highly susceptible to viral diseases that reduce growth, productivity, and post-harvest quality. Viral infections alter host physiological, biochemical, and molecular processes, resulting in huge economic losses, especially in vegetatively propagated fruit crops, where viruses spread rapidly through planting material and vectors. Recent developments in omics technologies, particularly proteomics and metabolomics, have transformed our understanding of plant–virus interactions by allowing detailed profiling of virus-induced molecular reprogramming. Proteomics reveals dynamic variation in host protein expression, which includes alterations in photosynthesis-related proteins, energy-metabolism enzymes, stress-responsive proteins, and components of defense pathways. Metabolomics complements this by detecting changes in primary metabolites such as sugars, amino acids, and organic acids, as well as secondary metabolites including phenolics, flavonoids, and alkaloids that control defense and symptom development. Integrated proteome-metabolome analyses highlight coordinated regulatory networks that control viral pathogenesis and host resistance mechanisms. These findings contribute to the discovery of early diagnostic biomarkers, the identification of resistance-associated molecules, and the development of tolerant cultivars through molecular breeding and biotechnology. Moreover, omics approaches can help improve post-harvest quality by elucidating metabolic and protein changes associated with ripening, senescence, and nutrient degradation. Despite their promise, challenges remain in standardization, data integration, and interpretation of complex datasets. Future efforts that combine artificial intelligence, multi-omics, and precision agriculture technologies will further enhance virus detection, disease forecasting, and sustainable fruit crop management. Overall, proteomics and metabolomics provide effective frameworks for understanding virus-induced changes and developing resilient fruit production systems.