IDO1 exhibits complex mechanisms of action and variable expression across different cancer types, presenting both challenges and opportunities. Its intricate mechanisms in tumor development and immune evasion pose significant challenges for translating IDO1 inhibitors into clinical drugs. However, recent advancements in AI-guided drug design, combination therapies, and improved drug delivery methods offer promising insights for enhancing IDO1 inhibitors, although further data is warranted. Despite these challenges, the increasing availability of IDO1 crystal structures and a deeper understanding of its biological roles support ongoing trials that combine IDO1 inhibitors with other therapies. These developments hold potential for improving therapeutic outcomes in cancer treatment. Moreover, the growing interest in applying IDO1 inhibitors to other diseases could stimulate further research and development of new IDO1 inhibitors, potentially benefiting their application in cancer therapy as well.