Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by a residual disease that results in relapse. This residual disease is often characterized by adaptive resistance that occurs via non-genetic mechanisms, and in melanoma involves altered metabolism. To examine how targeted therapy reprograms metabolism in BRAFV600 melanoma cells we employed a genome-wide screen for regulators of glycolysis and identified a role for selective mRNA export, transport and translation. Global poly-ribosome profiling confirmed extensive post-transcriptional reprogramming during the BRAF inhibitor response involving translational regulation and “buffering” of multiple metabolic pathways. We demonstrate that the lead candidate identified in our screen, the RNA processing kinase UHMK1, selectively associates with mRNA encoding metabolic proteins and regulates their nuclear export during the acute BRAFi response. UHMK1 is recruited to translating ribosomes upon BRAF inhibition and is essential for efficient synthesis of these metabolic proteins. UHMK1 depletion induces cell death by impairing glycolysis and mitochondrial oxidative metabolism, and importantly, genetic inactivation of UHMK1 delays resistance to MAPK pathway targeted therapy in vivo. Our data suggests UHMK1 regulates therapy-induced metabolic plasticity by controlling the abundance of metabolic enzymes through the export and translation of the mRNA that encode them. We propose a model wherein adaptive mRNA trafficking pathways contribute to metabolic plasticity underpinning targeted therapy response, and we suggest inactivation of these pathways may delay development of resistance to targeted therapies.