The present disclosure generally relates to instruction optimization (or otherwise improved execution of instructions) using voltage-based functional performance variation. In some examples, a method is described that includes instruction optimization (or otherwise improved execution of instructions) using voltage-based functional performance variation. In some examples, the method includes characterizing a workload for a multi-core processor to identify one or more subunits of individual cores of the multi-core processor for utilization by instructions included in the workload, selecting a voltage at which to operate cores of the multi-core processor, and assigning individual ones of the instructions of the workload to a core of the cores of the multi-core processor based on performance of the identified one or more subunits of the individual cores at the selected voltage.