Trees are essential to ecosystems in both natural and urban environments, yet they are increasingly threatened by abiotic and biotic stresses linked to climate change and human activities. The use of microbial-based approaches and microbiome engineering to safeguard plants and crop production is promising, but their application in trees raises specific challenges. Here, we review knowledge on the tree microbiome and outline opportunities to leverage tree-associated microbial communities. We describe the specific challenges inherent to working with tree species and highlight how Synthetic Microbial Communities (SynComs) can be used to study and engineer tree microbiomes. Finally, we propose that future research priorities include (1) developing model tree systems for experimental work, (2) obtaining tree-specific culture collections and SynComs, and (3) optimising methods for tree SynCom inoculation. Unlocking these methodological challenges will enable us to realise the potential of the tree microbiome and address global challenges in tree health and the provision of ecosystem services.