Introduction: Type 1 (T1D) and type 2 diabetes (T2D) are associated with an elevated incidence of infectious disease and a higher risk of infections-related hospitalization and death. Here, we delineated the “vaccinome” landscape obtained with a large immunization schedule offered by the Regional Government of Lombardy in a cohort of 618,396 patients with T1D and T2D. Methods: Between September 2021 and September 2022, immunization coverage for influenza, meningococcus, pneumococcus, and herpes zoster was obtained from the public computerized registry in 618,396 patients with T1D and T2D and in 9,534,087 non-diabetic subjects included in the healthcare system of Lombardy Region, Italy. Type of diabetes, age, mortality, and hospitalizations were retrospectively analyzed in vaccinated and unvaccinated patients. Results: Among patients with T1D and T2D, 44.6% received the influenza vaccine, 10.9% the pneumococcal vaccine, 2.5% the anti-meningococcus vaccine and 0.7% the anti-zoster. Patients with diabetes immunized for influenza, zoster and meningococcus showed a 2-fold overall reduction in mortality risk and a decrease in hospitalizations. A 3-fold lower risk of mortality and a decrease in hospitalizations for cardiac/pulmonary causes were also observed after influenza, zoster, and meningococcus immunization in older patients with T1D and T2D. Conclusions: Immunization coverage is still far from the recommended targets in patients with diabetes. Despite this, influenza vaccination protected nearly 3,800 per 100,000 patients with T1D and T2D from risk of death. The overall impressive decrease in mortality and hospitalizations observed in vaccinated patients strengthens the need for scaling up the “vaccinome” landscape in the diabetic population.