The present study was aimed at the formulation and evaluation of transdermal patches of Quetiapine fumarate to enhance its bioavailability and provide sustained drug release for improved therapeutic efficacy. Quetiapine fumarate, an antipsychotic agent with extensive first-pass metabolism and limited oral bioavailability, was selected as a suitable candidate for transdermal drug delivery. Patches were prepared by the solvent casting technique using polymers such as HPMC 15 cps, ethyl cellulose, and sodium carboxymethyl cellulose, with PEG 400 and glycerine as plasticizers, DMSO as a permeation enhancer and methanol: water (1:2). The formulated patches were evaluated for physicochemical parameters including thickness, weight uniformity, folding endurance, moisture content, and drug content uniformity. FTIR analysis confirmed the absence of drug–excipient interactions, indicating compatibility of the formulation components. In vitro drug release studies were carried out using phosphate buffer solution (pH 7.4) to assess drug release behaviour. Among all the prepared formulations, F4 was optimized, showing uniform thickness, adequate flexibility, good stability, and 90% drug content. In vitro diffusion studies revealed a sustained release profile with 82% cumulative drug release at 12 hours. Release kinetics indicated that the formulation followed the Higuchi model and the Hixson–Crowell model suggesting diffusion-controlled release with surface area–dependent dissolution. The findings confirm that Quetiapine fumarate can be effectively delivered through a transdermal patch system, offering advantages such as bypassing first-pass metabolism, reducing dosing frequency, and improving patient compliance. Thus, the developed formulation holds promise as a potential alternative to conventional oral therapy in the management of psychotic disorders.