The complex two-way relationship between diabetes mellitus (DM) and cancer poses a significant global health challenge. Shared mechanisms such as hyperinsulinemia, chronic inflammation, and oxidative stress create an environment that fosters cancer development, increasing the risk for certain cancers in individuals with diabetes, including pancreatic, colorectal, breast, liver, and endometrial malignancies. In this context, biomarkers emerge as essential tools, offering a means to untangle the connections between these two conditions by providing insights into early detection, diagnosis, prognosis, and treatment monitoring. For diabetic patients, biomarkers are particularly valuable as they help differentiate between changes caused by cancer and those driven by metabolic imbalances, illuminating disease evolution. This review examines the unique challenges encountered by diabetic patients with cancer, emphasizing the contributions of targeted biomarkers in identifying cancer subtypes, predicting outcomes, and guiding treatment decisions. We explore organ-specific biomarker profiles across various cancers, including pancreatic, colorectal, breast, liver, and lung, highlighting their potential to enhance diagnostic precision and enable personalized treatment strategies. Ultimately, we aim to illustrate how a deeper understanding of biomarker signatures can inform innovative clinical approaches and improve care for patients facing the dual burden of diabetes and cancer.