The Mar Menor, Europe’s largest saltwater lagoon in the Mediterranean basin (Murcia, southeastern Spain), is an ecosystem facing severe pollution, anoxia events, and marine biodiversity loss. This exploratory study examines the association between residential proximity to the Mar Menor and childhood cancer incidence in Murcia from 2000 to 2018. In our case–control study of 594 cancer cases and 3564 controls, matched by birth year and sex, participants were categorized by proximity to the lagoon (G1 ≥ 20 km, G2 = 10–20 km, G3 = 2–10 km, G4 = ≤ 2 km). Odds ratios (ORs) and 95% confidence intervals (95%CI) were adjusted for sociodemographic and environmental covariates. Analysis of distance as a continuous variable indicated a decrease both in all types of cancer and lymphoid acute leukemia risk with greater distance (OR = 0.99; 95% CI 0.98–0.99), while as a categorical variable, it revealed a non-linear pattern. Specifically, the risk did not increase for those living within 2 km of the lagoon (OR = 0.87; 95% CI 0.52–1.37), whereas increased risks were observed in the 2–20 km range within Campo de Cartagena (G2; OR = 1.32; 95% CI 1.01–1.73 and G3; OR = 1.43; 95% CI 1.00–2.02). This suggests modulating factors near the lagoon may counterbalance risks from broader environmental contamination. These findings highlight the complexity of environmental health dynamics and the importance of detailed research to guide public health strategies and urban planning for environmental and child health protection.