Background: Shift work is known to increase the risk of cardiometabolic diseases and mortality. We investigate the relationship between shift work schedules and cardiometabolic risk factors (smoking, hypertension, and obesity) and their association with cardiometabolic diseases (diabetes and cardiovascular diseases) in a multi-ethnic population from Singapore. Methods: 2469 participants from the Singapore-based Multi-Ethnic Cohort underwent physical and clinical assessments. Shift work schedules (morning, evening, night, and mixed) were assessed using a validated questionnaire. Results: Among shift workers, night shift workers had a significantly higher prevalence of smoking (54.5%), diabetes (27.3%), and cardiovascular events (14.1%). Compared to non-shift workers, workers in the night (OR = 2.10, 95%CI: 1.26–3.41) and mixed (OR = 1.74, 95%CI: 1.22–2.48) shift groups were more likely to be current smokers. A significant association between shift duration and smoking (OR = 1.02, 95%CI: 1.00–1.03) was also observed, with longer shift duration (in years) leading to an increase in smoking behavior. No significant associations were found between shift work schedules and hypertension, obesity (BMI), diabetes, and cardiovascular disease, as well as other cardiometabolic risk factors and diseases. Conclusion: This study found that shift schedules and shift duration were most strongly associated with smoking status after covariate adjustments (age, gender, ethnicity, socioeconomic status, and work arrangement), with night and mixed shift types being strongly associated with current smoker status. As smoking is a modifiable risk factor for cardiometabolic disease, employers of shift workers should increase work-based health interventions to control smoking and promote a healthier workforce.