As in the embedded systems domain, energy efficiency has recently become one of the main design criteria in high performance computing. The European Union Horizon 2020 project READEX (Run-time Exploitation of Application Dynamism for Energy-efficient eXascale computing) has developed a tools-aided auto-tuning methodology inspired by system scenario based design. Applying similar concepts as those presented in earlier chapters of this book, the dynamic behavior of HPC applications is exploited to achieve improved energy efficiency and performance. Driven by a consortium of European experts from academia, HPC resource providers, and industry, the READEX project has developed the first generic framework of its kind for split design-time and run-time tuning while targeting heterogeneous systems at the Exascale level. Using a real-life boundary element application, energy savings of more than 30% can be shown.