The objectives of the present studies were to develop the systematically optimized selfnanoemulsifying drug delivery systems (SNEDDS) of valsartan employing the holistic QbD approach. The quality profile target product (QTPP) was defined and critical quality attributes (CQAs) earmarked. Preformulation studies including the equilibrium solubility and pseudoternary phase titration studies facilitated the selection of suitable lipids and emulgents for formulation of SNEDDS. Risk assessment and factor screening studies facilitated the selection of Lauroglycol FCC and Capmul MCM L8 (i.e., lipid), Tween 40 and Tween 80 (i.e., emulgent) as the critical material attributes (CMAs) for SNEDDS prepared using medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs). A central composite design (CCD) was employed for systematic optimization of SNEDDS, taking globule size (Dnm), drug release in 10 min (Q10min) and amount permeated in 45 min (%Perm45min) as the CQAs. Design space was generated using apt mathematical models to embark upon the optimized formulations and validation of the QbD. In situ SPIP studies revealed significant improvement in the absorptivity and permeability parameters of SNEDDS owing to the inhibition of P-gp/MRP2 efflux vis-à-vis the conventional marketed formulation and pure drug. In vivo pharmacokinetic studies corroborated marked enhancement in the oral bioavailability drug from SNEDDS vis-à-vis the marketed formulation. Establishment of various levels of in vitro/in vivo correlations (IVIVC) indicated excellent goodness of fit between the in vitro drug release data with the in vivo absorption parameters. In a nutshell, the present studies report successful QbD-based development of MCT and LCT-SNEDDS of valsartan with improved biopharmaceutical performance.