Introduction: Paclitaxel is the most widely used taxane for treatment of tumor. It is marketed as Taxol__ampersandsignreg; wherein Cremophor EL and ethanol (50:50 v/v) are used as solubilizer. Cremphor is associated with severe side effects rendering Taxol__ampersandsignreg; clinically unacceptable. To overcome this limitation emulsomes are proposed to provide a biocompatible platform with the potential to en capsulate lipophilic drug in higher amount within its lipid core. Pharmaceutically stable emulsomal formulation can be prepared without the need of additional surfactant or solubilizer. Objective: The purpose of the present study was to design systematically optimized paclitaxel (Ptx) loaded, c(RGD) anchored emulsomes for effective tumor therapy to provide non-toxic alternative to the presently cremophor based Ptx formulation (Taxol). Method: Design expert__ampersandsignreg; 11 software was used for identifying the most significant variables using Taguchi orthogonal design (L8^2 array) followed by implementation of Box-Behenken design (3-level-4-factor) for precise optimization using PL:SL(X1 ), TL:SL (X2 ), Aqu:org phase volume (X3 ) and sonication time (X4 ) as independent variables. The response variables observed included particle size (PS), percentage entrapment efficiency (EE) and cumulative percentage drug release (DR). Results: Emulsomes has average particle size of 192.6__ampersandsignplusmn;0.450nm with PDI 0.226__ampersandsignplusmn;0.055, zeta potential of -33.86__ampersandsignplusmn;0.15mV and entrapment efficiency of 75.9__ampersandsignplusmn;3.55%. Formulation showed sustained drug release profile over 24 h at physiological pH and tumor pH. Slow release pattern could allow multi drug resistance (MDR) evasion, therefore enhancing the therapeutic efficacy of Ptx at lower dose. FACS analysis using A549 cell line showed higher uptake of RGD coated emulsome over plain emulsomes justifying the role of overexpressed integrin receptor in mediating receptor mediated endocytosis (RME). Conclusion: RGD anchored emulsomes could serve as biocompatible tumor specific delivery nanocarrier with improved drug entrapment and controlled release characteristics.