Nicotinamide N-methyltransferase (NNMT) converts nicotinamide (NAM) to 1-methylnicotinamide (1-MNA) using S-adenosylmethionine (SAM) as a methyl donor. NNMT has recently attracted increasing attention as it is highly expressed in liver tissues, adipose tissues and certain cancer tissues, and also exhibits increased expression in specific cells of patients with neurodegenerative diseases, obesity and diabetes. This article provides an overview of the role and associated upstream and downstream molecular pathways of NNMT in cancer cell migration and invasion, drug resistance, apoptosis, and autophagy, in an attempt to facilitate better understanding of the function and molecular mechanisms of NNMT in cancer initiation and progression.