Host-microbiome interactions are a critical component of host health, and plants have a particularly complex relationship with their microbiomes. Understanding these functional relationships will allow us to predict, and even influence, host fitness. Many ‘-omics’ techniques have been developed, and each is a powerful tool solo, but combining them opens the door to a more holistic, systems-level understanding. This strategy, called holo-omics, requires careful experimental design and faces several challenges as a field. First, it currently lacks well-tested analytical frameworks. Second, there is a need for freely available, specialized bioinformatics tools, as most focus on just one data source and don't integrate host and microbe data. Lastly, the heterogeneous nature of holo-omics data requires a wide range of expertise - including plant biologists, microbe experts, statisticians, and computational biologists. Holo-omics will likely be most useful in hypothesis generation and require experimental validation, but holo-omics remains a useful tool of understanding the basic biology of plant-microbe interactions, and the harmonization of techniques required to master holo-omics will have benefits for many research fields.