<p>Each individual is unique, and therefore, personalized treatment is the major focus of the current study. The contemporary work was undertaken to design 3D Printlet-Nano Intelligent Lipoidal System (3DP-NIL), accomplishing advanced statistical methodology. Trazodone (TZ), having poor aqueous solubility and dose variability with controlled release, was improved by solid intelligent nano-emulsifying drug delivery system (S-SNEDDS) and 3D printed dosage form, respectively. The proportion of varied components was selected to form SNEDDS based on solubility and ternary phase system. Quality by design was implemented to optimize TZ SNEDDS. The S-SNEDDS was loaded into 3-D printlet to form 3DP-NIL and characterized. The 3DP-NIL was developed. Oleic acid, Tween 80, and Transcutol P were screened as oil, surfactant, and co-surfactant for SNEDDS. 1:3 proportion of oil to <i>S</i>_mix was selected from ternary phase. Statistical design confirmed component crucial influence on SNEDDS. Optimal SNEDDS showed 205.2 nm size, 0.376 PDI, and − 30.7 mV zeta potential, confirmed stability, and nano-size. The results of differential scanning calorimeter, Fourier transform infrared spectroscopy, and X-ray diffraction established transformation of crystalline to amorphous assembly. Quality by design confirmed the relationship between chosen variables for 3DP-NIL. The 3DP-NIL controlled the release for 8 h with the desired mechanical strength. % Infill and layer thickness have the significant effect on the hardness and drug release of 3DP-NIL. The optimal 3DP-NIL has shown 5.55 hardness and 86.29% drug release. The solubility and functionality of TZ were improved by designing smart lipoidal formulation. Nano-sized uniform, stable, and immediate emulsion was formed. 3DP-NIL will satisfy requirement of patient customization with improved functionality.</p>