Maritime Spatial Planning (MSP) is bringing new challenges to planning and management in the marine realm, namely on the environmental assessment of the new plans and projects. Portugal is developing its first MSP instrument, PSOEM (Plano de Situação do Ordenamento do Espaço Marítimo), since 2015 and published it on December 2019. This paper focuses on a particular stage of the Strategic Environmental Assessment (SEA) of PSOEM regarding the assessment of the activities/uses that may significantly affect Natura 2000 marine network during the Plan's implementation in the Mainland subdivision. Over the years, progress has been made in researching and assessing the environmental impacts of maritime activities/uses. However, its application to practice raised several challenges and limitations. The methodological approach presented in this paper was developed to overcome knowledge, data and time constraints. Some of the limitations are a consequence of the MSP approach itself adopted in Portugal, namely the low technical detail on future uses and activities, which is required and desirable at this level of planning. Others relate with the lack of spatially explicit data on marine habitats and species distribution preserved under Natura 2000 network, which is not fully established in the marine environment. The adopted methodology started with the characterization and mapping of the conservation values and the pressures arising from the potential activities/uses. It followed with the assessment of their impacts and finally with the identification of mitigation measures, which were then adopted by the PSOEM as good practices. As new knowledge is generated and more information is collected, this tailor-made approach can be easily adapted and improved to keep supporting decision-making throughout PSOEM's implementation. The method can be easily adapted and transferred to other contexts, not only within the Portuguese maritime area, and could be made available to stakeholders that wish to invest in blue growth.