Abstract: Fedratinib is a selective Janus kinase-2 (JAK2) inhibitor indicated for the treatment of intermediate-2 and high-risk myelofibrosis. The present study aimed to develop and characterize controlled-release matrix tablets of Fedratinib using different concentrations of Ethylcellulose and Eudragit RS100 as release-retarding polymers by the direct compression method. Eight formulations (F1–F8) were prepared by direct compression using Ethylcellulose (F1–F4) and Eudragit RS100 (F5–F8). The prepared tablets showed acceptable weight variation, thickness, hardness, and friability within pharmacopoeial limits. Drug content ranged from 83.69% to 96.80%, with formulation F8 showing the highest drug content (96.80%). In-vitro dissolution studies revealed sustained drug release from all formulations over an 8-hour period. Formulation F8, containing the highest concentration of Eudragit RS100, exhibited the most desirable release profile with 99.55% cumulative drug release at the end of 8 hours. Drug release kinetic analysis indicated that the optimized formulation followed Zero-order kinetics (R² = 0.993) and showed a good fit to the Higuchi diffusion model (R² = 0.941), suggesting diffusion-controlled drug release. Stability studies conducted at 25°C/60% RH, 30°C/75% RH, and 40°C/75% RH for three months demonstrated no significant changes in drug release, confirming the stability of the optimized formulation.