The transition to sustainable transportation and the decarbonization of the waterborne sector represents significant global challenges. This study explores the potential of hydrogen as a zero-emission fuel for passenger vessels, addressing the need for an ecosystemic design methodology. By adopting a design-in-practice approach, the study presents a comprehensive methodology for hydrogen early-stage vessel design, streamlining the steps towards the IMO Alternative Design process. The study is part of EU-funded project e-SHyIPS, aiming to define the new guidelines for an effective introduction of hydrogen in the maritime passenger transport sector. Through theoretical studies, ship design experiments, feasibility, and safety system assessments, this research provides a methodology that serves as a guideline for maritime professionals. Furthermore, three case studies investigate the practical aspects of integrating hydrogen fuel cells into vessel architecture and their impact on performance and safety aspects. The findings of this research aim to facilitate the widespread adoption of hydrogen in waterborne transportation, significantly contributing to the European Green Deal and the International Maritime Organization’s decarbonization goals. By establishing a structured methodology and a supportive regulatory framework, the e-SHyIPS project supports the maritime industry’s transition towards sustainable and zero-emission practices.