The toxicological impact of exposure to chemical mixtures is a matter of undisputed concern, but mixtures are only slowly making their way into regulatory risk assessment. Critical knowledge gaps are which and how many chemicals drive mixture effects in the environment and in humans. Scientific uncertainty remains on the validity of the dose addition principle for complex mixtures of large numbers of chemicals at low concentrations as they occur in our bodies. The PANORAMIX consortium addresses these challenges by showcasing a novel experimental path based on whole mixture assessments for identifying and quantifying the risk of chemical mixtures extracted from real-life samples representing environment and food as well as humans. We provide ready-to-use and practical tools for mixture risk assessment of several chemicals with a diverse range of adverse health outcomes. The applied methodologies, including a panel of in vitro assays coupled with effect-directed analyses and large-scale suspect and non-targeted chemical profiling are innovative in their combinatorial approach. Specifically, we will take advantage of a well-studied human cohort of new-borns, in whom adverse health outcomes related to developmental toxicity originating from chemical mixture exposure will be identified. PANORAMIX will use mixture modelling, case studies and experimental data to deliver a web-based interface for calculating risks to chemical mixtures and to define effect-based trigger values for in vitro effects that can be directly measured in water, food, and blood to identify when mixture exposure is posing a health threat. By involving regulatory and scientific stakeholders throughout the project, we support the implementation of existing mixture risk assessment and management approaches to reduce the most critical exposures and assist in optimizing regulatory approaches to yield evidence-based policies, contributing to EU's zero-pollution ambition for a toxic free environment in the future.