Microplastics constitute an emerging contaminant of major concern in Latin America, where human exposure predominantly occurs through ingestion of drinking water and marine/estuarine food chains. This review synthesises available evidence on occurrence, exposure pathways, toxicological mechanisms, and regional public health risks, while examining regulatory and monitoring limitations that constrain effective risk management. Reported concentrations in drinking water show a wide range (1–1194 particles/L), dominated by PET, PP, and PS, with fibres and fragments as the main morphotypes. In commercial marine species, prevalence reaches 70–100%, with burdens up to 44 particles/g in oysters and ~90 particles/250 g in mussels. Estimated Daily Intake is 2–5 times higher in children (e.g., Chile: 13.03 vs. 5.59 particles/day in adults). Toxicological mechanisms include oxidative stress, chronic inflammation (NF-κB pathway), endocrine disruption, intestinal dysbiosis, systemic translocation, and placental transfer, exacerbated by vectorization of local co-contaminants (Hg from mining, Cd/Pb from agriculture). Risk indices indicate extreme danger in Brazil, Chile, and Ecuador, where data are available. Significant geographic and methodological gaps persist, with Brazil dominating research (~50–60%). Multicenter biomonitoring, harmonised surveillance networks, and SDG-aligned policies are urgently needed to reduce exposure burdens, protect vulnerable populations, and advance toward comprehensive regional risk assessment.