Cardiovascular disease (CVD) is a collective term for disorders of the heart and blood vessels. The molecular events and biochemical pathways associated with CVD are difficult to study in clinical settings on patients and in vitro conditions. Animal models play a pivotal and indispensable role in cardiovascular disease (CVD) research. Caenorhabditis elegans , a nematode species, has emerged as a prominent experimental organism widely utilised in various biomedical research fields. However, the specific number of CVD-related genes and pathways within the C. elegans genome remains undisclosed to date, limiting its in-depth utilisation for investigations. In the present study, we conducted a comprehensive analysis of genes and pathways related to CVD within the genomes of humans and C. elegans through a systematic bioinformatic approach. A total of 1113 genes in C. elegans orthologous to the most significant CVD-related genes in humans were identified, and the GO terms and pathways were compared to study the pathways that are conserved between the two species. In order to infer the functions of CVD-related orthologous genes in C. elegans, a PPI network was constructed. Orthologous gene PPI network analysis results reveal the hubs and important KRs: pmk-1, daf-21, gpb-1, crh-1, enpl-1, eef-1G, acdh-8, hif-1, pmk-2, and aha-1 in C. elegans. Modules were identified for determining the role of the orthologous genes at various levels in the created network. We also identified 9 commonly enriched pathways between humans and C. elegans linked with CVDs that include autophagy (animal), the ErbB signalling pathway, the FoxO signalling pathway, the MAPK signalling pathway, ABC transporters, the biosynthesis of unsaturated fatty acids, fatty acid metabolism, glutathione metabolism, and metabolic pathways. This study provides the first systematic genomic approach to explore the CVD-associated genes and pathways that are present in C. elegans, supporting the use of C. elegans as a prominent animal model organism for cardiovascular diseases.