To further prevent and reduce the pollution of air, water, and soil and to safeguard human health and well-being, the European regulatory framework needs to be improved to include a cross-regulatory approach. This scientific opinion paper presents such an approach for the systemic protection of air, water, soil and human health – the Zero Pollution Ambition Cycle developed by the German Environment Agency (UBA). The implementation of the measures announced by the European Commission within the EU Action Plan ‘Towards Zero Pollution for Air, Water and Soil’ published in May 2021 is an excellent opportunity for the different stakeholders for further developing and applying this integrated approach.