The article presents the results of an analysis of data obtained during a mass survey conducted in March-June 2023. The object is the working population aged 16 to 60, living in the Ural Federal District and working in various fields of employment: industrial production, mining, education, trade, healthcare, energy, state and municipal administration. The study used an online streaming sample. When forming the sample, a number of target parameters were controlled (screened sample) at the screening stage, which made it possible to ensure that the respondents corresponded to the object of the study: region of residence, actual employment, age, sector of employment. A total of 23,560 questionnaires were collected in 6 regions of the Ural Federal District. The structure of the developed toolkit consists of four blocks of questions and includes original developments and standardized methods aimed at studying various aspects of human well-being. The article presents the results obtained in the block on labor well-being. The analysis revealed gender differences in a number of factors influencing the well-being of workers in the context of the Fourth Industrial Revolution. The authors examined gender differences regarding the specifics of formalizing labor relations, enterprise restructuring, and wage reductions; analyzed the attitude of working men and women to the possibility of losing their jobs and the subjective perception of physical and psychosocial health in professional activities. The authors established that, at the present stage, the transformation of the world of work caused by the Fourth Industrial Revolution, although it did not cause a sharp deterioration in the well-being of workers, had a greater impact on the well-being of working women. Women are more likely than men to experience stress and negative emotions in the workplace; they face health problems caused by increased work intensity and more often express concern about the digitalization of work.