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Standard modifiable cardiovascular risk factors (SMuRFs) and non-SMuRFs are commonly used for risk stratification and therapeutic guidance after ST-elevation myocardial infarction (STEMI) in the general population. Their prognostic relevance with a potential implication for pharmacological and therapeutic management in individuals with established diabetes remains uncertain. This systematic review with meta-analysis aimed to identify prognostic factors associated with mortality in individuals with diabetes and STEMI qualifying for potential therapeutic targets. Studies evaluating prognostic factors for mortality in individuals with diabetes after STEMI were included up to May 3, 2025. Data extraction was performed independently by two reviewers. Certainty of evidence (CoE) was evaluated (GRADE). Thirty-seven studies were included, of which 25 had a high risk of bias. Mortality after STEMI in individuals with diabetes was consistently associated with non-SMuRFs (age, female sex, chronic kidney disease), acute cardiac dysfunction (Killip class III-IV, heart failure, cardiogenic shock), and atherosclerosis extent (anterior infarction, prior myocardial infarction, peripheral vascular disease). Diabetes-specific risk factors, including glycemic control parameters and insulin treatment, were also associated with increased risk of mortality (low to very low CoE). Once diabetes is established, no increased risk of mortality was observed for traditional SMuRFs, such as hypertension, smoking status, dyslipidemia, and obesity. These findings highlight the need for therapeutic strategies beyond conventional risk factor modification, with emphasis on acute hemodynamic management, tailored pharmacotherapy, and optimized glycemic control in this high-risk population. REGISTRATION PROSPERo: CRD42022378193.