Three decades of illegal practices of waste dumping and consequent environmental abuse have made the Campania region of Southern Italy a unique case in the context of waste-related health outcomes. Scientific evidence is mounting in support of a significant increase in cancer mortality and malformation occurrence in specific areas of the Campania region, where improper waste management and illegal waste trafficking have been repeatedly documented. However, the currently available evidence suffers from limitations mainly due to study design, lack of consideration of confounders and quality of the exposure data. Recent economic studies have shown the economic benefits of reclaiming toxic waste sites in Campania. Future perspectives include the adoption of different study designs, use of biomarkers and a molecular approach. Current knowledge, both scientific and economic, might be of help in orienting the short and long term governmental policy on waste related health outcomes at a regional level.