Within the confinements of critical infrastructures, the COVID-19 pandemic is posing a series of challenges to Health Management. In the spotlight of highly contagious and quick spreading diseases within such enclosed facilities, whether it be a detention facility or otherwise, the health and safety of those living within its internment is paramount. This paper aims to highlight the specific challenges and the possible solutions to counteract this problem, starting from the lessons learnt from the Italian prison system case study. Following the general description of the available resources within the Italian prisons, the study aimed at specifically describing the first counteracting measures deployed by the Italian prison authorities during the first phase of the COVID-19 outbreak (February–July 2020). The aim was to propose an integrated plan capable of responding to a biological threat within the prisons. In particular, the study describes the actions and technical features that, in accordance with national and international legal frameworks and the relevant organisational bodies that run the Italian Prison Service, had been adopted in managing, right from the start, the COVID-19 pandemic until Summer 2020. Available information and data showed the ability of the prison administration to comply almost completely with WHO’s technical and human rights recommendations and also, in successfully handling prison emergencies both in terms of the sick and the deceased in line with the epidemiological framework of the general population. In addition, the paper proposes a draft of guidelines that should involve the National Health Service and the Prison Service that are aimed at supporting the local prison facilities with drawing up their own biological incident contingency plans. An approved, legal, standardised plan could increase the awareness of prison managers. It could even increase their self-confidence, in particular, with regard to cases of dispute and their ability to respond to them. In fact, it is valuable and forward-thinking to be able to demonstrate that every endeavour has been taken and that ‘certified’ best practices have been put in place in accordance with the national standards.