Current environmental and climate changes are having a pronounced influence on the outcome of plant–pathogen interactions, further highlighting the fact that abiotic stresses strongly affect biotic interactions at various levels. For instance, physiological parameters such as plant architecture and tissue organization together with primary and specialized metabolism are affected by environmental constraints, and these combine to make an individual plant either a more or less suitable host for a given pathogen. In addition, abiotic stresses can affect the timely expression of plant defense and pathogen virulence. Indeed, several studies have shown that variations in temperature, and in water and mineral nutrient availability affect the expression of plant defense genes. The expression of virulence genes, known to be crucial for disease outbreak, is also affected by environmental conditions, potentially modifying existing pathosystems and paving the way for emerging pathogens. In this review, we summarize our current knowledge on the impact of abiotic stress on biotic interactions at the transcriptional level in both the plant and the pathogen side of the interaction. We also perform a metadata analysis of four different combinations of abiotic and biotic stresses, which identifies 197 common modulated genes with strong enrichment in Gene Ontology terms related to defense . We also describe the multistress-specific responses of selected defense-related genes.