IL-23 is a member of the IL-12 cytokine family and plays a central role in a group of immune-mediated inflammatory diseases (IMIDs), including psoriasis (PsO), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). IL-23 is produced by tissue-resident myeloid cells in response to tissue injury or pathogenic insults and promotes the expansion and survival of T helper 17 (Th17) cells, which produce inflammatory cytokines such as IL-17A. IL-23 also stimulates other immune cells, including γδ T cells, natural killer T cells, and innate lymphoid cells, which are collectively termed type-17 cells. IL-23 signaling is critical for the development and maintenance of these diseases, as it induces local tissue inflammation through the release of proinflammatory cytokines and suppresses regulatory T cells. IL-23 inhibition has shown significant clinical efficacy in treating PsO, PsA, and IBD, with improvements in clinical outcomes and long-term disease control. However, some patients show only partial responses, and the therapeutic benefit of IL-23 inhibition beyond these diseases is unclear. The role of IL-23 in maintaining barrier homeostasis in the skin and joints is less well understood. IL-23 is involved in host defense against certain pathogens and plays a key role in gut tissue homeostasis by supporting barrier function and tissue repair. IL-23 signaling pathways involve the IL-23 receptor and Janus kinases (JAKs), with TYK2 and STAT3 activation playing key roles in cytokine production. IL-23 inhibition has been shown to be effective in treating PsO, PsA, and IBD, with anti-IL-23 therapies approved for use in these conditions. However, the efficacy of IL-23 inhibitors may vary depending on the disease and patient population. Further studies are needed to better understand the molecular biology of IL-23, identify new therapeutic targets, and improve the effectiveness of IL-23 inhibition in treating IMIDs. A multiomics approach is proposed to advance the science of IL-23, including comprehensive studies to identify the spectrum of IL-23 receptor-expressing cells and provide insights into the role of IL-23 in driving IMIDs. Additionally, future research is needed to explore the durability of response, the potential for combination therapy, and the development of new IL-23 inhibitors. The role of IL-23 in other diseases, such as obesity, atherosclerosis, and cancer, is also being investigated. Overall, IL-23 inhibition has shown significant therapeutic potential in treating a range of IMIDs, but further research is needed to optimize its use and expand its applications.IL-23 is a member of the IL-12 cytokine family and plays a central role in a group of immune-mediated inflammatory diseases (IMIDs), including psoriasis (PsO), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). IL-23 is produced by tissue-resident myeloid cells in response to tissue injury or pathogenic insults and promotes the expansion and survival of T helper 17 (Th17) cells, which produce inflammatory cytokines such as IL-17A. IL-23 also stimulates other immune cells, including γδ T cells, natural killer T cells, and innate lymphoid cells, which are collectively termed type-17 cells. IL-23 signaling is critical for the development and maintenance of these diseases, as it induces local tissue inflammation through the release of proinflammatory cytokines and suppresses regulatory T cells. IL-23 inhibition has shown significant clinical efficacy in treating PsO, PsA, and IBD, with improvements in clinical outcomes and long-term disease control. However, some patients show only partial responses, and the therapeutic benefit of IL-23 inhibition beyond these diseases is unclear. The role of IL-23 in maintaining barrier homeostasis in the skin and joints is less well understood. IL-23 is involved in host defense against certain pathogens and plays a key role in gut tissue homeostasis by supporting barrier function and tissue repair. IL-23 signaling pathways involve the IL-23 receptor and Janus kinases (JAKs), with TYK2 and STAT3 activation playing key roles in cytokine production. IL-23 inhibition has been shown to be effective in treating PsO, PsA, and IBD, with anti-IL-23 therapies approved for use in these conditions. However, the efficacy of IL-23 inhibitors may vary depending on the disease and patient population. Further studies are needed to better understand the molecular biology of IL-23, identify new therapeutic targets, and improve the effectiveness of IL-23 inhibition in treating IMIDs. A multiomics approach is proposed to advance the science of IL-23, including comprehensive studies to identify the spectrum of IL-23 receptor-expressing cells and provide insights into the role of IL-23 in driving IMIDs. Additionally, future research is needed to explore the durability of response, the potential for combination therapy, and the development of new IL-23 inhibitors. The role of IL-23 in other diseases, such as obesity, atherosclerosis, and cancer, is also being investigated. Overall, IL-23 inhibition has shown significant therapeutic potential in treating a range of IMIDs, but further research is needed to optimize its use and expand its applications.