Cancer and diabetes are amongst the leading causes of deaths worldwide. There is an alarming rise in cancer incidences and mortality, with approximately 18.1 million new cases and 9.6 million deaths in 2018. A major contributory but neglected factor for risk of neoplastic transformation is hyperglycemia. Epidemiologically too, lifestyle patterns resulting in high blood glucose level, with or without the role of insulin, are more often correlated with cancer risk, progression, and mortality. The two conditions recurrently exist in comorbidity, and their interplay has rendered treatment regimens more challenging by restricting the choice of drugs, affecting surgical consequences, and having associated fatal complications. Limited comprehensive literature is available on their correlation, and a lack of clarity in understanding in such comorbid conditions contributes to higher mortality rates. Hence, a critical analysis of the elements responsible for enhanced mortality due to hyperglycemia-cancer concomitance is warranted. Given the lifestyle changes in the human population, increasing metabolic disorders, and glucose addiction of cancer cells, hyperglycemia related complications in cancer underline the necessity for further in-depth investigations. This review, therefore, attempts to shed light upon hyperglycemia associated factors in the risk, progression, mortality, and treatment of cancer to highlight important mechanisms and potential therapeutic targets.