Cancer metabolism is reprogrammed to fulfill the needs of proliferation and migration, which is accomplished through different levels of regulation. In recent years, new advances in protein post-translational modifications (PTMs) research have revealed a complex layer of regulatory mechanisms through which PTMs control cell signaling and metabolic pathways, contributing to the diverse metabolic phenotypes found in cancer. Despite the efficacy of current modeling approaches to study cancer metabolism they still lack the capacity to integrate PTMs in their predictions. Here we will review the importance of PTMs in cancer metabolic reprogramming and suggest ways in which computational predictions could be enhanced through the integration of PTMs.