Interactions between mitochondrial and nuclear genomes impact energy metabolism in many animal taxa. Presence of discrete mitochondrial genome dictates that maintenance of mitochondrial function involves close nuclear communication. Although selection is expected to maintain functional mito-nuclear interactions, we nonetheless see high levels of genetic polymorphism for these interactions. We also lack critical understanding of how this genetic variation affects energy metabolism, especially under environmental stress. The New Zealand mud snail Potamopyrgus antipodarum is well suited to answer these outstanding questions. The lakes inhabited by them span wide thermal gradients, with across-lake genetic structure that enables comparisons of metabolic responses in different mito-nuclear genotypes across environmental axes. Since mitochondria are maternally inherited, coexistence of sexual and asexuals in these snails presents contrasting systems of separate vs. co-inheritance of nuclear and mitochondrial genomes. As such, this snail provides a powerful means to dissect the evolutionary and functional consequences of mito-nuclear variation on energy metabolism. Here, we integrated cellular, physiological, and metabolomics approaches to quantify variation in energy metabolism across a diverse set of wild snail lineages. Our data provide important insights into complex relationships between mito-nuclear variation, metabolic plasticity, and fitness in natural populations. We also set the stage for applying this mollusk model system to answer broader questions including: 1) How do genomes give rise to complex organismal phenotypes? and 2) How do genomic processes linked to organismal function respond to ecological and evolutionary change?