We propose an ambitious yet well-conceived and deliverable pan-European, pan-cancer, pan-disciplinary, and multi-omic approach to address the pressing unmet need for an accurate, non-invasive, acceptable and cost-effective method of detecting precancerous and early-stage cancers in those individuals with Lynch syndrome (LS), the most common monogenetic increased hereditary cancer risk. LS has historically been underfunded and underserved, leading to significant an inequality in access and treatment. As a result, LS carriers have suffered needless cancers and deaths as a result. Our consortium has brought together the leading European experts, biotechnology companies and patient advocates to guarantee deliver practice-changing results that can be rapidly upscaled and adopted across the European Union and globally. Using an innovative clinical trial design, we will evaluate several multiple promising, non-invasive, liquid biopsy-based technologies in the three most common LS cancer types for an early-stage cancers detection. By leveraging Artificial intelligence (AI), we will identify traces of cancer, ensuring applicability to diverse healthcare systems. A comprehensive framework will assess the broader socio-economic and ethical impacts, ensuring that the solutions align with the societal values and healthcare needs. Parterning with leading biomarker companies (GNT, MSInsight, MSICare, MSIPlus and Elypta), we aim to deliver a multi-omic solution for affordable, accessible and effective test to advance the detection of heritable cancer detections in LS. This action is part of the Cancer Mission cluster of projects on “Prevention & early detection (early detection heritable cancers).