The global ocean faces increasing exploitation to meet the demand of a rapidly growing globalisation. Human marine activities are leading to local environmental pressures/benefits, for example on marine ecosystems and their services, but also through their value chains on terrestrial ecosystem services, and to global pressures such as global warming. Effective management of marine activities is essential for the conservation of the natural environment. There is a growing need for holistic sustainability assessment tools capable of quantifying environmental impacts at various geographical scales, alongside evidence-informed policies. This study examines the evolving marine policy landscape, identifies key legislation that supports the sustainable growth of the Blue Economy, traces its historical development, and explores the integration of ecosystem services assessment and life cycle assessment as methodologies for assessing environmental sustainability within this legislation. The review shows that current legislation falls short in providing instructions on how to measure sustainability impacts in a consistent way, i.e., which methods/indicators to use. Therefore, this study supports evidence-informed policy-making by proposing a quantitative and comprehensive environmental sustainability impact assessment methodology, integrating both ecosystem and life-cycle based methods, to a Belgian multi-use case study involving offshore wind energy and mussel farming. Considering the impacts that were possible to assess and the limits of the methodology used, the value of the positive impacts of the MUOF was +61.3 M€ y−, while the negative ones were −4.0 M€ y−1, resulting in a net handprint of +57.0 M€ y−1, primarily attributed to the benefits of the local ecosystem service ‘offshore renewable energy’ However, such a solution is not necessarily scalable, due to cumulative impacts. An analysis was conducted to identify areas for enhancing the methodology to more effectively meet policy needs. The study highlights the importance of using scientifically grounded methods to inform policy decisions.