The formal proof regarding key management and mutual authentication shows that this scheme has lightweight overheads in terms of energy, computation and communication costs, which is of interest for sustainable systems. In Contributions 12 and 13, the authors proposed other interesting applications of ML methods related to expert opinion and information security. In Contribution 14, the authors proposed a cyber-physical platform for the home appliance recognition and energy management of 5G (and 6G) communication infrastructure. In this article, a juxtaposed analysis is provided of the technologies, standards, and systems that are used. The performance analysis offers a recognition accuracy of 99% for home appliances compared with other related proposals. In Contribution 15, the authors proposed a simulation model to forecast the spread of the COVID-19 pandemic. The proposed model is derived from the Gaussian curve-fitting method using real data of the pandemic's evolution in Saudi Arabia. Social distancing measures have changed our lives, especially in densely populated cosmopolitan cities. Therefore, it is of great significance to accurately predict the Coronavirus pandemic using ML- and AI-based methods. In Contribution 16, the authors used ML methods to design intelligent systems for predicting dengue and cancer patients. In Contribution 17, the authors addressed the often-overlooked security and privacy issues associated with the medical IoT. In Contribution 18, the authors proposed a reliable mechanism for remote pain monitoring over wireless body area networks, which uses a trust management system to ensure the authenticity of the parties involved in the communication. The safety rate of the proposed system is reported to be 96%, which helps in the design of sustainable corporate systems. In Contributions 19-21, we found relevant applications of ML methods for the early classification, tracking, and prediction of diseases. The world must evolve to provide equitable access to unstructured big data from all corporate networks, including energy, transportation, information security, healthcare, and environmental sustainability. This shift requires smart solutions and sustainable networks to improve our living standards. The 21 articles in this Special Issue (listed in the following) demonstrate how modern applications of ML, AI, and IoT can help design useful systems that are increasingly important to our lives, health and well-being. Conceptualization: M.S., A.A., F.A. and J.-G.C. ; writing--original draft preparation: M.S., A.A. and F.A. ; writing--review and editing: J.-G.C. All authors have read and agreed to the published version of the manuscript. This research received no external funding. The authors declare no conflicts of interest. List of Contributions  
[PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON] Interpretable Machine Learning Models for Malicious Domains Detection Using Explainable Artificial Intelligence (XAI). _Sustainability_**2022**, _14_, 7375. [PERSON]; [PERSON]; [PERSON] [PERSON]; [PERSON]; [PERSON] [PERSON] An improved residential electricity load forecasting using a machine-learning-based feature selection approach and a proposed integration strategy. _Sustainability_**2021**, _13_, 6199. [PERSON]; [PERSON] [PERSON]; [PERSON]; [PERSON]; [PERSON]. A review of research works on supervised learning algorithms for SCADA intrusion detection and classification. _Sustainability_**2021**, _13_, 9597. [PERSON]; [PERSON]; [PERSON]; [PERSON] [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON] Student-performulator: Student academic performance using hybrid deep neural network. _Sustainability_**2021**, _13_, 9775. [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON] [PERSON]; [PERSON] A Novel Machine Learning-Based Price Forecasting for Energy Management Systems. _Sustainability_**2021**, _13_, 12693. [PERSON] [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON] [PERSON] A new efficient architecture for adaptive bit-rate video streaming.