As coral reef ecosystems experience unprecedented change, effective monitoring of reef traits supports management, conservation, and intervention efforts. There has been promising use in omics techniques to quantify key components of reef ecosystems that may serve as invisible sensors for reef health, dissolved metabolites and microorganisms. Dissolved metabolites are the chemical currencies released by reef organisms and transferred among microorganisms, contributing to nutrient cycling and signaling on reefs. Here we applied four omics techniques (taxonomic microbiome via amplicon sequencing, functional microbiome via shotgun metagenomics, targeted metabolomics and untargeted metabolomics) to waters overlying Floridas Coral Reef as well as microbiome profiling on corals from these reefs, to understand how microbes and dissolved metabolites reflect biogeographical, benthic and nutrient properties of this 500 km barrier reef. We show that the microbial and metabolite omics approaches each differentiated reef habitats, and that geographic zone had the most significant influence on microbial and metabolic characteristics. Further, seawater microbiome profiling and targeted metabolomics were significantly related to more reef and environmental characteristics compared to metagenomic sequencing and untargeted metabolomics. Within five coral species, microbiomes were also significantly related to reef zone, followed by species and disease status, suggesting that the water-based patterns in Florida also impact the reef builders. A combination of differential abundance and indicator species analysis revealed metabolite and microbial signatures of specific reef zones which demonstrate the utility of these techniques to provide new insights into reef microbial and metabolite traits which reflect broader ecosystem processes.