Landmark studies at the turn of the century revealed metabolic reprogramming as a driving force for lymphocyte differentiation and function. In addition to metabolic changes, differentiating lymphocytes must remodel their epigenetic landscape to properly rewire their gene expression. Recent discoveries have shown that metabolic shifts can shape the fate of lymphocytes by altering their epigenetic state, bringing together these two areas of inquiry. The ongoing evolution of high-dimensional cytometry has enabled increasingly comprehensive analyses of metabolic and epigenetic landscapes in lymphocytes that transcend the technical limitations of the past. Here, we review recent insights into the interplay between metabolism and epigenetics in lymphocytes and how its dysregulation can lead to immunological dysfunction and disease. We also discuss the latest technical advances in cytometry that have enabled these discoveries and that we anticipate will advance future work in this area.