Background: The Caserta and Naples areas in Campania Region experience heavy environmental contamination due to illegal waste disposal and burns, thus representing a valuable setting to develop a general model of human contamination with dioxins (PCDDs-PCDFs) and dioxin-like-PCBs (dl-PCBs). Methods: 94 breastfeeding women (aged 19–32 years; mean age 27.9 ± 3.0) were recruited to determine concentrations of PCDDs-PCDFs and dl-PCBs in their milk. Individual milk samples were collected and analyzed according to standard international procedures. A generalized linear model was used to test potential predictors of pollutant concentration in breast milk: age, exposure to waste fires, cigarette smoking, diet, and residence in high/low risk area (defined at high/low environmental pressure by a specific 2007 WHO report). A Structural Equation Model (SEM) analysis was carried out by taking into account PCDDs-PCDFs and dl-PCBs as endogenous variables and age, waste fires, risk area and smoking as exogenous variables. Results: All milk samples were contaminated by PCDDs-PCDFs (8.6 pg WHO-TEQ/98g fat ± 2.7; range 3.8–19) and dl-PCBs (8.0 pg WHO-TEQ/98g fat ± 3.7; range 2.5–24), with their concentrations being associated with age and exposure to waste fires (p