The use of biodegradable polymers is a good strategy to overcome challenges induced by petroleum‐based polymers. However, in general, there exist limitations in the formulation and fabrication of biodegradable polymers to be used in the development of parts with targeted applications. The issue is more highlighted when the 3D printing of biodegradable blends needs to be addressed. This study examines the formulation and fabrication of biodegradable nano‐reinforced polymer blends to be used in fused‐filament 3D printing. The melt‐mixing method was utilized to prepare filaments and nanocomposite systems of polylactic acid (PLA)/thermoplastic starch (TPS) blends reinforced with 0–5 wt% of nanoclay. To better understand the feasibility of the formulated compound, the process–structure–property interplays in the PLA/TPS based specimens fabricated via the fused‐filament 3D printing and injection molding were investigated and compared. The findings revealed the molded specimens showed greater tensile and flexural behavior than the printed specimens, whereas the impact resistance of the printed and molded parts was comparable. It was shown that increasing nanoclay content led to the increase in the tensile strength, Young's modulus and flexural strength of the specimens regardless of the method used. The greatest tensile strength of 10.1 and 20.1 MPa was revealed at the optimized nanoclay content of 1 and 3 wt% in 3D printed and molded parts, respectively. The surface morphology demonstrated that the addition of nanoclay favorably contributed to the interfacial adhesion, confirmed by the mechanical response of the specimens. It was shown nanoclay enhanced the thermal stability and crystallinity of the specimens while reducing water absorption and biodegradability due to its barrier properties.