Caves are ecosystems and natural heritage sites with magnificent biological diversity, from microorganisms to animals, despite their selective environment for development and survival. Until now, studies on cave microbiomes have included taxonomic classification through metagenomics analysis, demonstrating microbiological heterogeneity mainly composed of prokaryotic organisms or bacteria species. The generally oligotrophic environment, with limited energy input and dark zone, is the main feature differentiating the cave microorganisms from the other microbiomes and resulting in a unique habitat, which has unexplored regard to biology and chemical diversity. Multi-omics integration is a key strategy for scanning and integrating the macro and micromolecular universe, providing a better comprehension of processes and answers of the microbiome in natural cavities. Here, we highlight the strategies employed to study the cave microbiome, from the microbial genomes to their ability to secondary metabolites production, and also the multi-omics integration to explore the chemical and biological diversity in caves. animals survival now analysis species zone habitat Multiomics Multi omics universe cavities Here production multiomics multi caves