In nature, organisms are faced with constant nutritional options which fuel key life-history traits. Studies have shown that species can actively make nutritional decisions based on internal and external cues. Metabolism itself is underpinned by complex genomic interactions involving components from both nuclear and mitochondrial genomes. Products from these two genomes must coordinate how nutrients are extracted, used, and recycled. Given the complicated nature of metabolism, it is not well understood how nutritional choices are affected by mitonuclear interactions. This is under the rationale that changes in genomic interactions will affect metabolic flux and change physiological requirements. To this end we used a large Drosophila mitonuclear genetic panel, comprising 9 isogenic nuclear genomes coupled to 9 mitochondrial haplotypes, giving a total of 81 different mitonuclear genotypes. We use a capillary-based feeding assay to screen this panel for dietary preference between carbohydrate or protein. We find significant mitonuclear interactions modulating nutritional choices, with these epistatic interaction also being dependent on sex. Our findings support the notion that complex genomic interactions can place a constraint on metabolic flux. This work gives us deeper insights into how key metabolic interactions can have large implications on behaviour.