: The SARS-CoV-2 pandemic, since the beginning of 2020, has had a strong effect on many industry sectors including maritime transport. In this context, the passenger transport industry was the most affected and it is still in a very critical situation. Starting from the "No Sail Order" issued in March 2020, cruise companies stopped their operations. Besides the international regulatory bodies issued several guidelines for the prevention and management of pandemics onboard in order to safely resume cruises. The present work addresses this topic, aiming to discuss procedures and best practices to reduce the risk of uncontrolled spreading of SARS-CoV-2 infection on large cruise vessels. Starting from the lessons learned from the representative case of Diamond Princess, here the tools developed in the framework of Industry 4.0 have been used to highlight and handle the criticalities risen on the internal layout of passenger vessels, opening new opportunities to operate existing vessels and improve the design new buildings for outbreaks prevention and control.
