Increased risk of developing metabolic syndrome (MetS) has been associated with the APOA5, APOC1, BRAP, BUD13, CETP, LIPA, LPL, PLCG1, and ZPR1 genes. In this replication study, we reassessed whether these genes are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing MetS and its individual components. A total of 3,000 Taiwanese subjects were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our data showed a nominal association of MetS with the APOA5 rs662799, BUD13 rs11216129, BUD13 rs623908, CETP rs820299, and LIPA rs1412444 single nucleotide polymorphisms (SNPs). Moreover, APOA5 rs662799, BUD13 rs11216129, and BUD13 rs623908 were significantly associated with high triglyceride, low HDL, triglyceride, and HDL levels. Additionally, we found the interactions of APOA5 rs662799, BUD13 rs11216129, BUD13 rs623908, CETP rs820299, LIPA rs1412444, alcohol consumption, smoking status, or physical activity on MetS and its individual components. Our study indicates that the APOA5, BUD13, CETP, and LIPA genes may contribute to the risk of MetS independently as well as through gene-gene and gene-environment interactions.