Huge and ever-increasing energy consumption and consequent greenhouse gas (GHG) emissions pose unprecedented challenges to the sustainable development of the international human society. Our existing energy systems, where primary energy is converted to all sorts of final energy services, remain the major contributor to these global energy and environmental challenges. It is becoming a consensus that the conventional energy conversion and utilization mode should make place for a more sustainable one with higher energy conversion efficiency, lower air pollutions and GHG emissions, less dependence on fossil fuels, and more utilization of renewable energy. However, although there exist many technical options and technology pathways to enable this transition, they are usually treated separately by their very own technical communities and political groups without coordination with others, and the overall effect and potential is therefore greatly constrained as compared to a systematic approach where all alternatives are taken into consideration in an integrated way. Energy systems engineering provides a methodological modeling and optimization framework to address the complex energy and environmental problems existed in design and operation of energy systems in an integrated manner. This methodological framework is generic, and it can help to produce optimal design and operational plans for energy systems ranging from nanoscale, microscale, mesoscale, to mega-scale levels over operating horizons from milliseconds to months and years. This Article first gives a brief overview of typical methodologies of energy systems engineering, comprising superstructure based modeling, mixed-integer linear and nonlinear programming, multiobjective optimization, optimization under uncertainty, and life-cycle assessment. The concept of energy systems engineering and these methodologies are further illustrated via their applications in some typical real-life energy systems of very different nature and scale, ranging from polygeneration energy systems, hydrogen infrastructure planning, energy systems in commercial buildings, and biofuel supply chains.