Cardiovascular diseases (CVDs) still remain the leading concern of global health, accounting for approximately 17.9 million deaths in 2016. The pathogenetic mechanisms of CVDs are multifactorial and incompletely understood. Recent evidence has shown that alterations in the gut microbiome and its associated metabolites may influence the pathogenesis and progression of CVDs such as atherosclerosis, heart failure, hypertension, and arrhythmia, yet the underlying links are not fully elucidated. Owing to the progress in next-generation sequencing techniques and computational strategies, researchers now are available to explore the emerging links to the genomes, transcriptomes, proteomes, and metabolomes in parallel meta-omics approaches, presenting a panoramic vista of culture-independent microbial investigation. This review aims to outline the characteristics of meta-omics pipelines and provide a brief overview of current applications in CVDs studies which can be practical for addressing crucial knowledge gaps in this field, as well as to shed its light on cardiovascular risk biomarkers and therapeutic intervention in the near future.