As a potent antioxidant with numerous health benefits, lycopene finds multiple applications. Among the geometric isomers of lycopene, the Z-isomers have greater bioavailability than the all-E-isomer but are less stable and hence, less suitable for practical applications. Herein, highly stable Z-isomer-rich lycopene nanodispersions are produced through the thermal isomerization of (all-E)-lycopene in a flow reactor followed by continuous dispersion in an aqueous emulsifier (Tween 20, sucrose fatty acid ester, or polyglycerol fatty acid ester [PFAE]) solution upon agitation with an in-line swirl mixer. The effects of emulsifier type and other processing conditions (flow rate, pressure, temperature, lycopene Z-isomer ratio) on dispersion efficiency and properties are examined in detail, and finally, Z-isomer-rich lycopene nanodispersions (>60% of total Z-isomer ratio and <10 nm of mean particle size) are successfully obtained. Moreover, it is found that lycopene Z-isomers have greater encapsulation efficiency for dispersions with emulsifiers than that of the all-E-isomer. The storage test of the resulting dispersions clearly shows that the highest storage stability is achieved in the case of using PFAE, which effectively inhibits lycopene degradation and reverse (Z- to all-E) isomerization. Practical applications: To practical use of lycopene Z-isomers, it is essential to improve their storage stability as well as usability (i.e., dispersibility in water). The present study reveals that when producing the lycopene dispersions, the use of PFAE as an emulsifier allows to improve the stability of lycopene isomers and inhibit the Z- to all-E-isomerization during storage. Given the high demand for stable Z-isomer-rich lycopene formulations, the obtained results promote the practical use of lycopene Z-isomers in diverse (e.g., food and cosmetic) industries.