The dual climate change and biodiversity crises put an urgency for implementing inclusive, just, and effective policies, while their inextricable nature calls for integrated assessment approaches that capture synergies and trade-offs. Mainstream economic methods currently used in the appraisal of environmental policies fail to capture the complexity of the climate-biodiversity-economy nexus. Even though uncertainty, disruption, and irreversibility are inherent to environmental challenges, these are overlooked when designing and evaluating the performance of policies. Policy effectiveness and resilience against other impact areas, such as quality of life, financial stability, political feasibility, innovation is not included in policy appraisal. Rather, policy evaluation is informed by a narrow set of metrics, falling short of encompassing broader considerations of sustainability and wellbeing. DECIPHER employs a systems and multi-disciplinary approach using a diverse set of models, methods, and processes to significantly improve decision-making on climate change and biodiversity and enhance policy resilience and feasibility. Moving beyond state-of-the-art, we will establish a holistic and operational decision-making framework that integrates advanced economic and biophysical models, empirical methods and stakeholder participation tools. The novel framework incorporates environmental damages in the economic decisions of agents and introduces a risk-opportunity approach for decision making. To offer critical insights on system dynamics and risks, the models developed will be equipped with innovative features including improved representations of agent behavior, technology innovation, financial risk valuation and the capacity to assess extreme events and critical tipping points. The new decision-making framework will be the end-result of an iterative co-creation process with stakeholders and applied under real-world conditions in the assessment of flagship EU policies.