The poor permeability of antipsychotics hinders schizophrenia treatment through the blood-brain barrier due to tight junctions and P-glycoprotein efflux. Intranasal microemulsions offer a promising route for direct nose-to-brain transport through olfactory and trigeminal pathways, potentially improving therapeutic outcomes. This study aims to elucidate how varying concentrations of surfactant–co-surfactant mixtures (Smix) influence the physicochemical attributes and release kinetics of clozapine-loaded microemulsions, to identify optimised formulation parameters for enhanced stability and therapeutic performance. Microemulsion formulations were developed employing Tween 80 as the surfactant, oleic acid as the oil phase, and PEG 400 as the cosurfactant. The Smix ratio was systematically varied, and the resulting formulations were characterised for droplet diameter, polydispersity index (PDI), pH, viscosity, conductivity, refractive index, and optical transparency. In-vitro release profiles were subsequently assessed using the dialysis bag diffusion technique. The formulations exhibited high transmittance, nasal-compatible pH values (5.2–5.7), and viscosities ranging from 11.4 ± 1.6 to 410.3 ± 2.5 cP. Droplet sizes were between 13.5 and 200.8 nm with a PDI < 0.3, indicating uniform size distribution. In-vitro release studies revealed sustained drug delivery over 24 h. Increasing the Smix concentration from 20% to 60% significantly enhanced the cumulative drug release rate from 62.3 ± 0.3% to 99.8 ± 0.4% (p < 0.05), reduced droplet size, and increased viscosity. Variation in Smix concentration is a pivotal factor in customising the physicochemical characteristics and release behaviour of clozapine microemulsions. Optimising this parameter may facilitate the development of effective intranasal formulations for targeted nose-to-brain transport, thereby advancing therapeutic strategies for schizophrenia management.