Human genetic analyses and epidemiological studies showed a potential association between several types of gene polymorphism and the development of coronary heart disease (CHD). Many studies on this pertinent topic need to be investigated further to reach an evidence-based conclusion. Therefore, in this current review, we describe several types of gene polymorphisms that are potentially linked to CHD. A systematic review using the databases EBSCO, PubMed, and ScienceDirect databases was searched until October of 2022 to find relevant studies on the topic of gene polymorphisms on risk factors for CHD, especially for the factors associated with single nucleotide polymorphisms (SNPs). The risk of bias and quality assessment was evaluated by Joanna Briggs Institute (JBI) guidelines. From keyword search results, a total of 6243 articles were identified, which were subsequently narrowed to 14 articles using prespecified inclusion criteria. The results suggested that there were 33 single nucleotide polymorphisms (SNPs) that can potentially increase the risk factors and clinical symptoms of CHD. This study also indicated that gene polymorphisms had a potential role in increasing CHD risk factors that were causally associated with atherosclerosis, increased homocysteine, immune/inflammatory response, Low-Density Lipoprotein (LDL), arterial lesions, and reduction of therapeutic effectiveness. In conclusion, the findings of this study indicate that SNPs may increase risk factors for CHD and SNPs show different effects between individuals. This demonstrates that knowledge of SNPs on CHD risk factors can be used to develop biomarkers for diagnostics and therapeutic response prediction to decide successful therapy and become the basis for defining personalized medicine in future.