This study aims to characterise and assess the stability of an optimised lignocaine-adrenaline nanogel using central composite design (CCD). Compatibility studies were conducted using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) and Ultraviolet-visible (UV-vis) spectroscopy. Eighteen lignocaine-adrenaline Nanoemulsion (LANE) formulations derived using CCD were characterised for particle size, polydispersity index (PDI), zeta potential and pH. All LANE formulations were transformed into lignocaine-adrenaline Nanoemulsion-based Gel (NBG) by adding 0.1 % Carbopol 940. Stability studies for LANE and NBG were conducted for 12 months storage at 25 °C. The results of long-term stability assessment of LANEs and NBGs were integrated with CCD predictions to produce the optimised NBG, lignocaine-adrenaline Nanogel. The optimised NBG model was validated in triplicates. The optimised NBG was subjected to 5000 rpm centrifugation for 30 min, repeated heating-cooling cycles (40 °C and 4 °C), and a freeze-thaw cycle (-5 °C and 25 °C). ATR-FTIR and UV-vis results indicated compatibility between lignocaine, adrenaline and the excipients. The viscosity of the nanogel corresponded to that of ferric sulphate solution (24 ± 1 mPa·s at 20 °C). The LANE and NBG formulations showed no drug precipitation or phase separation after the stability study. The optimised NBG had particle size (61.76 ± 0.25 nm), PDI (0.36 ± 0.01), zeta potential (-26.47 ± 0.02 mV) and pH (6.28 ± 0.02). The optimised NBG remained stable in stress-induced environments. CCD enabled optimisation of a stable NBG formulation.