The proceeding presents best selected papers presented at 5th International Conference on Smart Computing and Informatics (SCI 2021), held at Department of Computer Science and Engineering, Vasvi College of Engineering, Hyderabad, Telangana, India, during 17 – 18 September 2021. It presents advanced and multi-disciplinary research towards the design of smart computing and informatics. The theme is on a broader front focuses on various innovation paradigms in system knowledge, intelligence and sustainability that may be applied to provide realistic solutions to varied problems in society, environment and industries. The scope is also extended towards the deployment of emerging computational and knowledge transfer approaches, optimizing solutions in various disciplines of science, technology and healthcare. The work is published in two volumes.