Removable dental prostheses remain a reliable treatment for edentulous patients. Conventional fabrication requires multiple steps, whereas computer-aided design and manufacturing (CAD-CAM), particularly 3D printing, offers faster and more cost-effective alternatives. This in vitro study aimed to evaluate the effect of sandblasting on surface roughness and shear bond strength of silicone soft liner bonded to 3D-printed and heat-cured acrylic denture base materials. Eighty specimens were divided into four groups: heat-cured control, 3D-printed control, heat-cured sandblasted, and 3D-printed sandblasted. Surface roughness was measured using a profilometer, while shear bond strength was tested with a universal testing machine. Data were analyzed with one-way ANOVA and Games-Howell post hoc test. Sandblasting significantly increased both surface roughness and shear bond strength compared to untreated groups. The 3D-printed specimens showed higher roughness values after sandblasting than heat-cured ones. Sandblasting improves surface roughness and bonding performance of both heat-cured and 3D-printed denture base resins, supporting its use as an effective surface treatment in prosthodontics.