The field of Oceans and Human Health (OHH) is an emerging discipline that requires novel, interdisciplinary approaches to address the ecological and public health consequences of our changing oceans. As population growth and development continue to increase in coastal zones, there is an urgent need to reduce anthropogenic impacts on marine ecosystems. This research is framed around the premise that the increasing availability of environmental genomic sequence data in tandem with the advancing bioinformatics now offers high-throughput and systems-based approaches and opportunities for environmental health monitoring. Specifically, we hypothesize that environmental genomic information can provide sensitive and functional markers of human impacts on marine ecosystems which can then be used to improve our understanding of how the composition of micro-organism communities relates to public health. We utilize a gene-environment approach whereby the complex interplay between genetic and environmental factors in marine ecosystems can provide insight into potential OHH concerns including chemical and pharmaceutical pollution. Three case studies are presented that incorporate comparative genomic, metagenomic and decision-analysis methodologies. First, a comparative genomic approach is used to investigate the G protein-coupled receptor signaling pathway in marine diatoms. This pathway plays an important role in the genomic underpinnings of mammalian environmental response, and thus its presence and potential functionality in environmental perception and response to stressors in these crucial primary producers is of interest. Secondly, metagenomics in combination with next generation sequencing is used to profile the microbial composition and antibiotic resistance determinant signals across differentially impacted environments, including marine, nearshore and wastewater ecosystems. The environment serves as a reservoir for resistance genes that can be disseminated to pathogenic bacteria in clinical settings, but baseline data is needed for the prevalence and distribution of these genes and the genomic vectors that transfer these genes across environmental bacteria. Thirdly, this metagenomic data is conceptually framed within a public health screening framework by incorporating the data into an index for surveillance of antibiotic resistance determinants in the environment. Metagenomic screening of genomic markers relevant to public health may serve as an early risk management approach that can trigger further monitoring and analysis.