Accelerated energy demands, together with unprecedented CO2 emissions, aggravate the global energy and climate change crises, endangering the sustainable development of society in a perpetuity way. The ability to find, extract, and use energy in an effective and clean way is pivotal to the energy paradigm shift, where a large percentage of global energy demand is expected to be met through sustainable energy resources. Research in materials science is contributing towards such a sustainable future by addressing bottleneck questions in energy storage and conversion, which are two main parts of energy sustainability. In particular, recently discovered two-dimensional (2D) materials exhibit extraordinary mechanical, chemical, electronic, optical, and magnetic properties that are promising to break through current material limitations in energy applications. The main goal of this thesis is to examine the possibility of using 2D materials in improving current energy applications, in particular, battery electrodes and hydrogen evolution reaction (HER) catalysts, and to elucidate the mechanisms and guiding principles in tuning 2D materials using combinatorial simulation techniques that bridge different length scales. Representative and promising 2D material systems, including graphene-like materials, MXenes, transition metal dichalcogenides (TMDs), layered covalent-organic framework (COF), and oxides are studied. To evaluate the performance of 2D materials in battery electrodes, we employ the density functional theory (DFT) simulations to investigate the adsorption of different metal ions onto 2D MXenes and 2D graphene-like materials, and hence quantify the enhanced theoretical capacities and rate-performance. Moreover, we find the origin of such improvements and summarize guiding principles in tuning 2D materials for similar applications in batteries beyond lithium. We also show that 2D TMDs are capable of improving hydrogen production efficiency. The role of defects and electronic coupling between substrate and MoS2 catalysts is investigated, followed by a study of using the Janus asymmetry as a feasible way to activate basal plane catalytic activity. Finally, we present a multiscale modeling method that bridges different length scales, and show several successful examples in applying this method in energy applications. This thesis provides new understandings of 2D materials in energy applications. Such understandings may be used to accelerate the realization of future energy plan.