Parasitic infections remain highly prevalent worldwide and contribute substantially to chronic morbidity in endemic regions. Increasing evidence suggests that certain parasites are etiologically linked to human malignancies, while the long-term oncologic impact of antiparasitic drug exposure remains uncertain. This systematic review and meta-analysis aimed to evaluate associations between parasitic infections, antiparasitic drug exposure, and cancer risk. A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Scopus was conducted from inception to December 2025. Observational studies reporting associations between confirmed parasitic infection or antiparasitic drug exposure and incident cancer were included. Random-effects meta-analyses were performed where comparable effect estimates were available. Fifty-two studies met inclusion criteria, of which twenty-eight were eligible for quantitative synthesis. Liver fluke infection (Opisthorchis viverrini and Clonorchis sinensis) was strongly associated with cholangiocarcinoma (pooled OR 4.82; 95% CI 3.21–7.24). Chronic Schistosoma haematobium infection was significantly associated with bladder cancer (pooled OR 3.17; 95% CI 2.11–4.76), with a stronger association observed for squamous cell carcinoma. The association between Schistosoma mansoni and colorectal cancer was modest and not statistically significant (pooled OR 1.42; 95% CI 0.98–2.06). In contrast, pooled analyses of antiparasitic drug exposure—including praziquantel, albendazole/mebendazole, and ivermectin—demonstrated no increased overall cancer risk. Heterogeneity across studies was moderate for infection-related analyses and low for drug exposure analyses. These findings confirm strong associations between specific parasitic infections and site-specific malignancies, consistent with established carcinogenic classifications. Evidence for other parasite–cancer links remains inconclusive. Importantly, therapeutic antiparasitic drug exposure does not appear to increase long-term cancer risk. Effective control and treatment of carcinogenic parasitic infections should be considered an integral component of global cancer prevention strategies.