In coastal waters worldwide, an increase in frequency and intensity of algal blooms has been attributed to eutrophication, with further increases predicted because of climate change. Yet, the cellular-level changes that occur in blooming algae remain largely unknown. Comparative metatranscriptomics was used to investigate the underlying molecular mechanisms associated with a dinoflagellate bloom in a eutrophied estuary. Here we show that under bloom conditions, there is increased expression of metabolic pathways indicative of rapidly growing cells, including energy production, carbon metabolism, transporters and synthesis of cellular membrane components. In addition, there is a prominence of highly expressed genes involved in the synthesis of membrane-associated molecules, including those for the production of glycosaminoglycans (GAGs), which may serve roles in nutrient acquisition and/or cell surface adhesion. Biotin and thiamine synthesis genes also increased expression along with several cobalamin biosynthesis-associated genes, suggesting processing of B12 intermediates by dinoflagellates. The patterns in gene expression observed are consistent with bloom-forming dinoflagellates eliciting a cellular response to elevated nutrient demands and to promote interactions with their surrounding bacterial consortia, possibly in an effort to cultivate for enhancement of vitamin and nutrient exchanges and/or direct consumption. Our findings provide potential molecular targets for bloom characterization and management efforts.