Low-grade systemic inflammation is an important determinant of chronic disease risk and long-term workers’ health outcomes. The neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective haematological biomarker that reflects systemic inflammatory status and may be influenced by modifiable lifestyle factors. This study examined the association between smoking behaviour, physical activity, and systemic inflammation among mining workers. A cross-sectional analytical study was conducted using periodic medical check-up data from 567 bauxite mining workers in Indonesia collected between June 2023 and January 2024. Multiple linear regression analysis was performed while controlling for age, body mass index (BMI), and length of employment to minimise potential confounding effects. The regression model was statistically significant (p < 0.001; Adjusted R² = 0.190), indicating that the included variables explained a meaningful proportion of variance in NLR. Physical activity showed a significant negative association with NLR (β = −0.366; p < 0.001), whereas smoking behaviour (β = 0.202; p < 0.001) and age (β = 0.115; p = 0.003) were positively associated with systemic inflammation. BMI and years of service were not significant predictors in the final model. These findings suggest that lifestyle factors, particularly physical activity and smoking, play an important role in systemic inflammation among mining workers. Integrating targeted lifestyle interventions into occupational health programmes may help reduce inflammation-related health risks and improve long-term workforce sustainability.