Genistein (Gen) is a naturally occurring soy isoflavonoid, ing anticancer, antiproliferation & antioxidant-like properties which make it suitable as an anticancer medicine. The disadvantage of poor solubility and less oral bioavailability restrict its use as potential anticancer agent. In the present study, Gen was entrapped into solid-liquid lipid mixture with the aid of surfactant by using modified solvent evaporation technique. The present work was carried out with the aim to screen the component as well as process variables to ease the formulation process which ends up with the finished product having characteristics of best nanoformulation in all respects. Optimized levels by employing numerical optimization technique for each factor viz. surfactant concentration (X1), Lipid concentration (X2) & amount of organic solvent (X3) were 0.3 %, 0.78 % & 8.51 ml respectively. The resultant formulation exhibited a particle size of 122.22 nm, and entrapment efficiency of 92.8 %, & zeta potential of-21.25 mV with unimodal size distribution. Findings of the haemocompatibility studies suggested that optimized formulation was pretty safe for intravenous administration. In a nutshell, GenNLC seems to be a superior alternative carrier system for the formulation industry to obtain the higher entrapment with excellent stability of the formulation.