Marine Protected Areas (MPAs) are a tool to safeguard marine natural systems, yet their effectiveness depends on how well they are integrated into the existing socioeconomic context. Stakeholder engagement in MPA design can contribute to increasing integration. This study focuses on the co-design of an MPA between researchers, public administration, the private sector, and non-governmental organizations. The proposed MPA is in Portugal and includes an area that is a hotspot for biodiversity and economic activities. This is the first MPA proposal in mainland Portugal co-designed using a participatory approach. This study highlights the steps of the zoning process and synthesizes the eight main lessons learned, useful for other cases, particularly for relatively small coastal MPAs with multiple socioeconomic activities. Three zoning proposals were developed and discussed within the participatory process. The proposals considered the best scientific and local knowledge available and were defined using ecological, socioeconomic, and shape-area guiding principles. In an iterative manner and following a participatory approach, compromises with stakeholders were achieved, and a final proposal, scientifically sound and socially accepted by most stakeholders, was delivered to the government. The final zoning plan will achieve ambitious conservation goals, including the largest fully protected area to be declared in mainland Portugal, while minimizing the impacts on the existing economic activities and promoting its sustainability. This process resulted in valuable lessons that may be applied elsewhere and guide future MPA implementation or rezoning of existing ones. These transdisciplinary and participatory processes can be time and resource-consuming but are vital for ensuring MPA effectiveness.