Industry 4.0 makes a factory smart by applying advanced information systems and future-oriented technologies. Today, thanks to the application of the most innovative digital technologies offered by the new Industry 4.0 paradigm, in this Fourth Industrial Revolution, there is a significant "evolution" of many methodologies of Continuous Improvement, such as, e.g., Lean Six Sigma (LSS). Most of the tools of Lean Six Sigma relies on data to know in depth problems: data is necessary to drive any process improvement. The key issue is based on data integrity and on real time data. The aim of this paper consists of proving the efficiency of the so called "Lean Six Sigma 4.0". This paper deals with engineering approaches, here applied in HealthCare environment, in order to optimise the services supply process and to reduce the waste of resources (human and/or material), while improving the Quality of Experience (QoE) of the patients. Indeed, it has been proved that the huge growth in the HealthCare costs is due to inefficient use of available resources and not-optimised service processes. Applying Lean Six Sigma 4.0 it is possible to reduce HealthCare costs, improving at the same time the QoE perceived by the patient.