Objectives: This study investigated the conjointly negative effects of floating shift work and physical inactivity on fatty liver disease (FLD) using ultrasound- based hepatic steatosis assessment. Material and Methods: Weighted multivariable logistic regression models were used to evaluate associations between work shifts, physical activity (PA), and FLD. Stratified and subgroup analyses were conducted to assess effect modification. Linear and quadratic regression models explored threshold effects of metabolic equivalent task (MET) levels on the degree of hepatic steatosis across shift types. Results: Data from 653 participants revealed that compared with the control group (controlled attenuation parameter – CAP <248), the case group (CAP ≥ 248) had a significantly higher prevalence of floating shifts (53.8% vs. 43.5%, p = 0.008) and physical inactivity (27.8% vs. 19.1%, p = 0.032). In multivariable-adjusted models, floating shifts independently increased FLD risk (odds ratio (OR) = 1.40, p = 0.019), while PA showed a borderline association with lower FLD risk (OR = 0.57, p = 0.056). Strikingly, compared to the reference group (physically active day-shift workers), physically inactive floating-shift workers had a higher risk of FLD (OR = 2.01, p = 0.049), highlighting the effects of occupational and behavioral factors. Subgroup analyses identified advanced age (OR = 2.42, p = 0.034), obesity (OR = 12.87, p < 0.001), hypertension (OR = 2.66, p = 0.028), and diabetes (OR = 6.21, p = 0.017) as critical risk factors among floating shift workers. At moderate METs (200–400 h/week), CAP values between floating and day shift workers converged with minimal differences in the quadratic regression model. Sensitivity analyses confirmed the robustness of the primary findings: the FLD risk persisted after excluding liver diseases and with an alternative PA definition (≥22 MET-h/week). A stricter CAP threshold attenuated the shift work association. Notably, adjusting for dietary pattern attenuated but did not eliminate the significant link between shift work and FLD (OR = 1.39, p = 0.030). Conclusions: These findings emphasize the urgent need for workplace interventions targeting shift schedules to mitigate FLD risk, particularly in high-risk occupational populations. Int J Occup Med Environ Health. 2026;39(3)