Imidafenacin tablets are the first-line drug for the treatment of overactive bladder (OAB). However, the tablets need to be taken twice daily for up to 3-6 months, which highly reduces patient compliance. This study aimed to develop a long-acting imidafenacin transdermal patch (LAITP) with high drug loading using amorphous solid dispersion technology (ASD). ASD, consisting of polyvinyl pyrrolidone and imidafenacin, not only significantly increased the drug loading in the patch, but also inhibited drug crystallization. Furthermore, the formation mechanism of ASD was systematically elucidated using SEM, XRD, DSC, FT-IR, and molecular docking. The LAITP was optimized through single-factor investigations and ternary phase diagram analysis. It was confirmed by SEM and confocal Raman microscopy that ASD was a spherical microparticle with a size of 28.62 ± 8.91 µm in LAITP. Notably, under long-term and accelerated conditions of 3 months, the LAITP exhibited excellent stability to ensure the reliability of quality. Importantly, human pharmacokinetic studies demonstrated that LAITP with low skin irritation and favorable adhesion properties prolonged sustained effective plasma concentration in comparison to commercial tablets (Staybla®), reducing the frequency of administration and thereby improving patient compliance, which is expected to be a promising treatment option for patients with OAB.