Ubiquitination represents one of the most critical post-translational modifications, comprising a multi-stage enzyme process that plays a pivotal role in a myriad of cellular biological activities. The deregulation of the processes of ubiquitination and deubiquitination is associated with the development of cancers and other diseases. This typescript reviews the impact of ubiquitination on metabolic processes, elucidating the regulatory functions of ubiquitination on pivotal enzymes within metabolic pathways in pathological contexts. It underscores the role of ubiquitination-driven metabolism disorders in the etiology of cancers, and oncogenesis, and highlights the potential therapeutic efficacy of targeting ubiquitination-driven enzymes in cancer metabolism, their combination with immune checkpoint inhibitors, and their clinical applications.