Pain is a prevalent symptom among cancer patients and survivors. Psychoactive substance use (PSU) is associated with both the presence and severity of pain. However, little is known about this association in the context of cancer. The primary objective was to compare the prevalence of PSU and its relationship with pain during and after cancer. PSU was defined as the use of nonmedication substances (alcohol, tobacco, e‐cigarettes, cannabidiol, and cannabis), with frequency categorized as at least yearly, monthly, weekly, or daily. Secondary objectives aimed to explore the relationships between PSU and pain characteristics, health‐related quality of life, anxiety, depression, deprivation, and individual characteristics. Among the 1041 individuals included, pain prevalence was 44.7% (95% confidence interval [CI] 41.6%–47.8%). The overall prevalence of PSU at least monthly was 67.0% (95% CI 64.0%–69.8%). The proportions of chronic and neuropathic pains were higher for at least monthly use of cannabidiol compared to nonuse (70.0% vs. 39.3% and 55.7% vs. 28.1%, p < .001). In multivariate analysis, the monthly uses of tobacco and cannabidiol were higher in painful individuals than in nonpainful ones (odds ratio: 2.85 [95% CI 1.22–6.64] and 3.76 [95% CI 1.13–12.44], p < .05). From the point of view of the patient care, the study underscores the need for physicians to prioritize smoking cessation and pay attention to the use of cannabidiol during and after cancer.