Aim: One major challenge associated with the design of transdermal drug delivery systems is to overcome the barrier of the skin. Hence, current study aimed at hydrogel based nanoemulsion (HNE) of lercanidipine for enhanced transdermal delivery and investigation for its rheology, bioadhesion, droplet size, transmission electron microscopy (TEM), and skin permeation mechanism.Main Methods: Flow behavior of HNE was studied by conducting the controlled stress rate study using R/S CPS plus Rheometer and Bio-adhesive strength was measured by texture analyzer. Skin permeation mechanism across rat skin was determined by differential scanning calorimeter (DSC) study, activation energy (Ea) determination, histopathological examination, confocal laser scanning microscopy (CLSM). Moreover, we have used TEM and Biovis IP2000 software for microscopic analysis. Key Finding: The formulation exhibited HershelBulkley flow with good bioadhesion (43N/mm). A uniform droplets distribution under TEM image with size of 80.18±0.315nm inside gel network was found. DSC, Ea and histopathological examination revealed that HNE might have dissolved intercellular lipid and separated corneocytes from each other to weaken the barrier function of SC for enhancing the skin permeation. CLSM result dictated a distributed droplets throughout the skin layers with high depth of penetration (>150.0 μm). Significance: The formulation has a good perspective to safe and effective delivery of lercanidipine for enhanced transdermal application.