The emerging intertwined activities of metabolism and epigenetics unveils culprits and prospects in cancer.

The vast majority of cellular processes are interconnected in a manner that facilitates the overall function of the cell within its tissue environment. It has become evident that the dynamic interplay between metabolic processes and the regulation of genomic activities, including gene expression, is contingent on metabolite levels and factors that govern cellular distribution and compartmentalization. The advent of rapid technological and biophysical advances over the past two decades has yielded a compendium of factors, including metabolites and genes, that have provided extensive insight into their interrelationship. Here we discuss and summarize the many metabolites that have been experimentally shown to directly influence chromatin factors and epigenetic patterns. We aim to provide a comprehensive overview of the temporal and spatial dynamics of these processes within the cell, emphasizing the significance of metabolite abundance and the intricate orchestration of these processes during ontogeny and disease progression. The influence of lifestyle factors, such as diet and environmental exposures, on metabolite levels and their potential implications for therapeutic interventions is a subject of particular interest. The intricate interplay between metabolism and the epigenome in cancer offers a fertile ground for further research. By elucidating the manner in which metabolic fluctuations influence the epigenetic landscape, novel therapeutic approaches that target both metabolic and epigenetic pathways may emerge as promising avenues for cancer treatment.