Endometriosis is a benign disease affecting one in ten women of reproductive age worldwide. Although the pain level is not correlated to the extent of the disease it still is one of the cardinal symptoms strongly affecting the patients’ quality of life. Yet, a molecular mechanism leading to the formation of severe pain remains to be defined. Recent studies have indicated a close interaction between newly generated nerve cells and macrophages, leading to neurogenic inflammation in the pelvic area. In this context, the responsiveness of an endometriotic cell culture model was characterized upon inflammatory stimulation by employing a multi-omics approach, including proteomics and metabolomics. Differential proteomic profiling of the 12-Z endometriotic cell line treated with TNFα and IL1β unexpectedly showed that the inflammatory stimulation was able to induce a protein signature associated with neuroangiogenesis, specifically including neuropilins (NRP1/2). Untargeted metabolomic profiling in the same setup further revealed that the endometriotic cells were capable of the autonomous production of 7,8-dihydrobiopterin (BH2), 7,8-dihydroneopterin and epinephrine. These metabolites are related to the development of neuropathic pain and the former two were even up-regulated upon the inflammatory stimulation. Thus, the inflammatory stimulation of endometriotic 12-Z cells led to protein and metabolite expression changes that strongly suggest a direct involvement of epithelial cells in endometriosis pain development.