In recent years, the interaction mechanisms underpinning the synthetic microbial co-culture systems have gained increasing attention due to their potentials in various biotechnological applications. Exploration of the inter-species mechanisms underpinning the synthetic microbial co-culture system could contribute to a better understanding of the theoretical basis to further optimize the existing co-culture systems, and design new synthetic co-culture system for large-scale application. OMICS technologies such as genomics, transcriptomics, proteomics, and metabolomics could analyze the biological processes in a high throughput manner. Multi-omics analysis could achieve a "global view" of various members in the microbial co-culture systems, which presents opportunities in understanding synthetic microbial consortia better. This article summarizes recent advances in understanding the mechanisms of synthetic microbial co-culture systems using omics technologies, from the aspects of metabolic network, energy metabolism, signal transduction, membrane transport, stress response, community stability and structural rationality. All these findings could provide important theoretical basis for future application of the microbial co-culture systems with the aids of emerging biotechnologies such as synthetic biology and genome editing.