Dendritic cell (DC) activation by contact allergens is one of the key steps in the development of allergic contact dermatitis (ACD). Recent evidence suggests that metabolic reprogramming is a prerequisite for the activation of DCs, macrophages and monocytes. Therefore, we used an integrated approach by combining proteomics and metabolomics to investigate the metabolism of human THP-1 cells in response to the strong contact allergen, 2,4-dinitrochlorobenzene (DNCB). Cells were treated with 5, 10 and 20 μM DNCB for 4, 8, and 24 h, respectively. Using a targeted metabolomics approach, we quantified levels of 188 endogenous metabolites, among them phospholipids, acylcarnitines, amino acids and hexoses. In addition, proteomic changes were analyzed using an untargeted quantitative approach based on stable isotope labeling with amino acids in cell culture (SILAC). We detected several alterations in the metabolome and consistently in the proteome indicating metabolic reprogramming of THP-1 cells by DNCB. In particular, we found an increase in phospholipids that was accompanied by an up-regulation of fatty acid synthase (FAS), a key enzyme in lipid synthesis.