Energy systems are the major contributor to ever-increasing primary energy consumption and consequent greenhouse gas emissions. To tackle these critical problems, planning and design of energy systems needs to be improved towards a more efficient, cost-effective, and environmentally benign direction. However, although there are many technical choices available, they are often developed separately by their own technical communities and driven by their specific interest, thus methods and experience obtained in planning and design of a certain type of energy systems are usually not applicable to other types of energy systems. Energy systems engineering provides a generic methodological framework to facilitate the planning and design of energy systems and to produce integrated solutions to real-life complex energy problems via a systematic approach.In this paper, we present an overview of key methodologies of energy systems engineering, covering superstructure based modelling, mixed-integer programming, multi-objective optimization, optimization under uncertainty, and life-cycle assessment. Applications of these methodologies in polygeneration energy systems design, hydrogen infrastructure planning, and design of energy systems in commercial buildings are provided to demonstrate the capability of these methodologies.