Additive manufacturing allows for designing innovative properties to pharmaceutical products. Binder jetting (BJ) 3D printing is one of the key techniques within innovative manufacturing. In this study, a structured approach according to the Quality by Design (QbD) principles was implemented to explore the factors affecting fabrication of drug-loaded products produced by BJ 3D printing. The investigated factors included the weight ratio of binder in primary powder and the process parameters related to printing (layer thickness and number of layers). Critical quality attributes, namely disintegration time, tensile strength, friability, dimensions (diameter and height accuracies), residual water content, weight and drug loading were determined based on the quality target product profile of a tablet analogue. The experimental results with a 2-level full factorial design were modeled by multiple linear regression. It was found that binder content was an important factor determining the integrity of the printed products, and the formation of the microstructure of the product was affected by multiple material properties and process parameters. QbD is a systematic and effective approach providing mechanistic understanding of BJ 3D printing and allowing for an efficient design of products with the desired quality.