Objectives: This study aimed to assess the prevalence and risk factors associated with disease-related malnutrition (DRM) in hospitalized patients using the Subjective Global Assessment (SGA) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Additionally, we sought to identify key determinants of moderate and severe malnutrition. Methods: A retrospective analysis was conducted on 1036 adult patients hospitalized in a tertiary care hospital between August 2019 and November 2020. Nutritional status was evaluated using both the SGA and GLIM criteria. Data on demographic characteristics, comorbidities, dietary intake, and gastrointestinal symptoms were collected. Logistic regression models were employed to identify risk factors for DRM, and multivariate analysis was used to determine independent predictors. Results: The prevalence of DRM was 63.3% according to GLIM and 64.8% according to SGA. Moderate malnutrition was observed in 22.6% of patients, while 40.7% were classified as having severe malnutrition, and severe weight loss was noted in 34.5% of the subjects. The key risk factors for DRM included male sex (OR 1.67, p < 0.0001), non-oncological gastrointestinal conditions (OR 1.48, p = 0.041), infectious diseases (OR 1.66, p = 0.007), inadequate ingestion (OR 5.13, p < 0.0001), and the presence of gastrointestinal symptoms (OR 3.06, p < 0.0001). Individualized diets were found to have a protective effect, while central parenteral nutrition significantly reduced the risk of severe DRM (OR 0.610, p = 0.014). In the final adjusted model, sex (p < 0.0001), ingestion (p < 0.0001), and gastrointestinal symptoms (p < 0.0001) emerged as the most significant independent predictors of DRM. Conclusions: The high prevalence of DRM in hospitalized patients emphasizes the importance of routine nutritional screening and personalized interventions. Proactive management of key risk factors such as inadequate intake and gastrointestinal symptoms is crucial to mitigating malnutrition and improving patient outcomes.