Adrenocortical carcinoma is a rare malignancy with aggressive behavior and poor prognosis since the diagnosis is made in an advanced and metastatic stage in most patients. To date, conventional chemotherapies allow a response only in a reduced percentage of cases. For this reason, attention has focused on the opportunities provided by immunotherapy, taking as example its application for the treatment of other types of cancer. An increasing number of studies have investigated the composition and functioning of the tumor microenvironment in various solid tumors that emerged as a major determinant of cancer response in immunotherapy, with the attempt to manipulate immune mechanisms in favor of the host. We will try to elucidate the potential applications and the limits of immunotherapy in adrenocortical carcinoma suggesting additional therapeutic approaches. Immunotherapy with immune checkpoint inhibitors employed in combination with classical chemotherapy could potentially improve clinical outcome in advanced stages of adrenocortical carcinoma. However, many efforts should still be spent to identify new targets and specific drugs.