Most of the cancer patients have multiple comorbid conditions, commonly diabetes mellitus, hypertension, and coronary vascular diseases. Cancer treatment involves a multidisciplinary approach targeting primary cancer-directed therapy along with optimal management of comorbid conditions as well. Hyperglycemia, which exists prior to cancer therapy initiation or if it develops during or after therapy, is associated with less desirable outcomes like treatment compromise due to increased adverse effects of therapy and higher mortality. Hence, prompt diagnoses and management of hyperglycemia become crucial during therapy. Healthcare providers working in an oncology setting, as well as primary care providers, should be aware of medications that are associated with hyperglycemia and diabetes. This paper will elucidate various cancer-directed therapies associated with hyperglycemia.