The article is devoted to the quantitative assessment of the impact of human-centered design of automated workplaces on occupational safety, organizational culture, and quality economics of an industrial enterprise in the context of the transition to the Industry 5.0 paradigm. The aim of the study is to establish statistically substantiated relationships between the ergonomic parameters of the work environment, indicators of employee engagement, and financial results, including quality costs, productivity, and economic value added. The empirical base was formed by data from 142 enterprises of the automotive, precision instrument engineering, and pharmaceutical industries in Eastern Europe and Asia for 2019–2023, combining financial and production reporting, occupational safety protocols, telemetry of automated workplaces, and survey results of more than 3,500 operators and 400 line managers. An integral human-centered design index (HCD-Index) is proposed, including 24 indicators of physical, cognitive, and interface ergonomics measured using eye-tracking, heart rate sensors, force platforms, and standardized questionnaires, as well as a safety culture index (SCI); the data were analyzed using multiple regression, factor and variance analysis, and Monte Carlo modeling. It is shown that an increase in the HCD index is accompanied by a statistically significant reduction in operation cycle time, defect rate, and the number of safety incidents, a decrease in the cost of rework, and an increase in NOPAT and EVA, with a payback period for ergonomic investments of about 1.5 years. It has been established that the configuration high automation level — standard HMI with low human centeredness increases the severity of incident consequences and expected economic damage, whereas the implementation of adaptive interfaces and cognitive ergonomics radically reduces the risk of catastrophic failures despite the inevitable rise in the cost of downtime for high-tech lines. A strong inverse relationship has been found between the level of safety culture and the cost of nonconformities, confirming the multiplicative effect of combining human-centered design and a developed organizational culture on the stability of production results, reduction of variability in key performance indicators, and enhancement of the enterprise’s investment attractiveness. It is concluded that investments in human-centered design and safety culture should be regarded as a strategic element of business value management and that relevant indicators should be included in the system of corporate reporting and management KPIs.