||Background This study assessed the associations of short-term employment, physical and psychological occupational demands, and job dissatisfaction with alcohol abuse (using the Audit-C test) and daily smoking among working French men and women in different age groups. Methods The sample included 13,241 working people, 18–29, 30–39, and 40–59-years-old, randomly selected in France and interviewed by phone. Occupation, type of employment, physical demands, psychological demands, job dissatisfaction, gender, age, educational level, and income were considered. Data were analyzed with logistic models. Results Alcohol abuse affected 20.4% of men and 7.5% of women; smoking 32.1% and 24.2%, respectively. Their patterns of association with the occupational factors varied with gender and age. Job dissatisfaction was the leading factor among young men (adjusted odds ratio for alcohol abuse and smoking: 1.71 and 2.02), whereas short-term employment was the leading factor among young women (1.69 and 1.58), this pattern being reversed in older generations. The pattern of associations of physical and psychological demands with outcomes is more complex, but overall psychological demands were more important for women (especially the younger ones) than men, especially for smoking (OR > 1.6). Smoking within 5 min after waking was much more common among male and female smokers with these occupational factors, suggesting a potential dependency. Conclusions Workers with short-term employment and occupational demands are subject to a higher risk for alcohol abuse and smoking with high gender and age disparities. Gender and age should be considered when designing measures to prevent substance abuse related to occupation.