Background <p>Infertility is a major public health concern worldwide, with growing evidence implicating environmental exposures to heavy metals as potential contributors. This systematic review and meta-analysis aimed to evaluate the association between heavy metals in biological samples and infertility among men and women.</p> Methods <p>Following PRISMA guidelines, a systematic search on PubMed, Scopus, and Web of Science was conducted. Observational studies reporting levels of arsenic, cadmium, chromium, mercury, nickel, and lead in infertile versus fertile individuals were included until December 2025. Data screening, data extraction and quality assessment was performed by two researchers independently. Heterogeneity between studies was assessed using Cochran’s Q test and the I² statistic. Meta-analysis was performed using fixed/random-effects model to pool standardized mean differences (SMD) and 95% confidence intervals (CI).</p> Results <p>A total of 22 studies were included in the systematic review. In the qualitative synthesis, although the association of infertility with different heavy metals was statistically significant in the most of included studies, the findings were heterogeneous among studies. In the quantitative synthesis, seminal levels of cadmium (pooled SMD = 1.84, 95% CI: 0.15, 3.53), blood lead levels (SMD = 0.69, 95% CI: 0.06, 1.32), and blood mercury concentrations (SMD = 0.16, 95% CI: 0.02, 0.30) was significantly higher in infertile individuals compared with fertile counterparts. Other pooled associations between heavy metals and infertility were not statistically significant (<i>p</i> &gt; 0.05).</p> Conclusion <p>The study findings support a significant association between heavy metals, particularly cadmium, lead and mercury with infertility. These findings underscore the importance of mitigating environmental and occupational exposure to heavy metals to protect reproductive health.</p>