Forest tree diseases pose a significant threat to the health and sustainability of forests due to climate change, human-driven deforestation, and global trade, which can introduce invasive pathogens. As forests’ environmental and economic importance becomes increasingly obvious, developing effective strategies to combat these diseases is imperative. Biotechnology offers innovative and sustainable solutions for the management and mitigation of tree diseases. The multi-omics approach involves integrating data through different omics fields, including genomics, transcriptomics, proteomics, and metabolomics, to realize a wider insight into biological systems. By analysing plants’ genetic, transcriptomic, proteomic, and metabolomic profiles and associated microbes, we can gain insights into the mechanisms underlying plant-microbial interactions and develop predictive models for managing plant diseases under changing environmental conditions. Marker-assisted breeding is a powerful method for enhancing breeding programs’ efficiency by using DNA markers associated with loci or QTLs of interest. Marker-assisted selection has been widely implemented to introduce disease resistance genes into susceptible lines of several commercial crop species. It also allows for gene pyramiding to broaden the disease tolerance spectrum. This chapter comprehensively explores genetic resistance and marker-assisted selection (MAS), genome editing, RNA interference (RNAi), plant immune system activation and omics approaches in forest disease management. These approaches not only contribute to disease control but also promote the preservation of biodiversity and the overall health of forest ecosystems.