Infertility represents a reproductive public and health issue. Males account for 50% of infertility cases, often considered idiopathic. Single-nucleotide polymorphisms (SNPs) have been investigated in relation to non-obstructive azoospermia (NOA), especially the folate enzymes molecular pathway. This systematic review and meta-analysis aims to evaluate the relationship between SNPs and NOA susceptibility. PubMed, Scopus, and Web of Science were searched for studies published in English up to October 2022. Case-control studies focusing on SNPs in folate metabolism enzymes were assessed for eligibility. The Q-Genie tool was used to assess the quality of the included studies’ quality. SNPs examined in more than two studies for the same genotype underwent random-effect meta-analyses, yielding pooled odds ratios (ORs) and 95% confidence intervals (CIs). I2 statistic was utilized to evaluate heterogeneity. Out of 697 search outputs, 13 articles were included, all of good quality, conducted in Caucasian (61.5%) and Asian (38.5%) ethnicity. Eight SNPs were identified and meta-analysis was conducted on four of them. The pooled ORs of SNPs and NOA were: for rs1801133 1.33 (95% CI: 1.02-1.74, I2 64.7%) for CT genotype, and 2.03 (95% CI: 1.25-3.28, I2 75.1%) for TT genotype; for rs1801131 0.99 (95% CI: 0.78-1.25, I2 23.5%) for AC genotype, and 1.01 (95% CI: 0.65-1.57, I2 0%) for CC genotype; for rs1801394 was 1.15 (95% CI: 0.79-1.68, I2 0%) for AG genotype, and 1.12 (95% CI: 0.61-2.05, I2 0%) for AA genotype; for rs1805087 1.47 (95% CI: 1.05-2.05, I2 0%) for AG genotype, and 4.28 (95% CI: 2.17-8.44, I2 0%) for GG genotype. We report a significant association between rs1801133 and rs1805087 SNPs and NOA. However, to determine the use of these SNPs for genetic testing in clinical and public health practice, more research is required. Identifying populations at higher risk of infertility could guide personalised preventive and diagnostic programs.