Reprogramming of cancer cell metabolism and nutrient acquisition underpins several important tumourigenic processes, including proliferation, metastasis and therapeutic resistance. In addition, there is growing evidence that non-cancer cell types within the tumour microenvironment may also undergo metabolic reprogramming so as to support cellular processes that facilitate tumour growth. Cancer-associated fibroblasts (CAFs) are a class of non-cancer cell that are activated in response to diverse cues within the tumour niche. Once activated, CAFs may promote tumour progression through a range of functions, including shuttling nutrients to cancer cells and modulating immune infiltration. Notably, a subclass of TGFb-induced CAFs known as myoCAFs play a critical role in depositing and remodelling collagenous extracellular matrix (ECM) in the tumour microenvironment. This myoCAF-mediated dysregulation of ECM architecture is a key feature of most solid tumours, and promotes pro-oncogenic signalling and local invasion of cancer cells. Although ECM production is known to be a metabolically demanding process, little is known about the specific metabolic pathways that are reprogrammed during myoCAF activation. Using an in vitro model of mammary myoCAF activation, we have interrogated transcriptomic changes that occur during the process of TGFb-mediated myoCAF induction. RNAseq analyses revealed that the metabolic enzyme N-nicotinamide methyltransferase (NNMT) is upregulated in both TGFb-treated fibroblasts and mature myoCAFs relative to untreated mammary fibroblasts. Notably, upregulation of NNMT is shown to occur downstream of TGFb-dependent induction of the master metabolic regulator, activating-trancription factor 4 (ATF4). Using RT-PCR, immunoblotting and collagen remodelling assays, we were also able to show that genetic knockdown of both ATF4 and NNMT abrogate myoCAF activation and function. Together, these data suggest that a TGFb-ATF4-NNMT axis underlies the activation of normal mammary fibroblasts to myoCAFs. By better understanding this mechanism of CAF activation, we hope to elucidate strategies for targeting tumour progression at the microenvironmental level.