Chemicals are part of our daily lives and we are exposed to numerous chemicals through multiple pathways. Relevant scientific evidence contributing to the regulation of hazardous chemicals require a holistic approach to assess simultaneous exposure to multiple compounds. Currently, the main way to obtain data on the exposure to organic chemicals is through human biomonitoring, that requires very complex and costly sampling campaigns. Finding efficient proxies to predict the risk of chemical exposure in humans is an urgent need to cover large areas and populations at a reasonable cost. We conducted a study to characterize the human chemical exposome in maternal blood and placenta samples of a population-based birth cohort in Barcelona (2018-2021, n>300). Ultimate HRMS-based approaches were applied including wide-scope target, suspect (for >2300 and >10000 chemicals, respectively) and non-target screening. More than sixty chemicals were identified including pesticides, personal care products or industrial compounds, among others, in the range of ng/mL and ng/g. In parallel, sewage sludge from the wastewater treatment plants serving the residence areas of the studied population were also screened, showing correlations with the type and concentrations of chemicals found in humans. Our findings were suggestive for the potential use of sewage sludge as a proxy of the human exposure and its application in early-warning systems to prevent chemical threats.