PI3K/AKT/mTOR signaling pathway plays a vital role in the development and progress of pheochromocytoma. However, blocking one of the targets alone may activate the feedback loop of upstream targets and the parallel signaling pathways, which causes the resistance to PI3K/AKT/mTOR pathway inhibitors. This paper reviews the role of PI3K/AKT/mTOR signaling pathway in the development and progress of pheochromocytoma and latest research progresses of relevant targeted therapies, especially targeted therapies combined with multi-target and multi-pathway.