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Background: Precision interventions using biological data may enhance smoking treatment, yet are understudied among smokers who are disproportionately burdened by smoking-related disease.

Methods: We surveyed smokers in the NCI-sponsored Southern Community Cohort Study, consisting primarily of African-American, low-income adults. Seven items assessed attitudes toward aspects of precision smoking treatment, from undergoing tests to acting on results. Items were dichotomized as favorable (5 = strongly agree/4 = agree) versus less favorable (1 = strongly disagree/2 = disagree/3 = neutral); a summary score reflecting generalized attitudes was also computed. Multivariable logistic regression tested independent associations of motivation (precontemplation, contemplation, and preparation) and confidence in quitting (low, medium, and high) with generalized attitudes, controlling for sociodemographic factors and nicotine dependence.

Results: More than 70% of respondents endorsed favorable generalized attitudes toward precision medicine, with individual item favorability ranging from 64% to 83%. Smokers holding favorable generalized attitudes reported higher income and education (P < 0.05). Predicted probabilities of favorable generalized attitudes ranged from 63% to 75% across motivation levels [contemplation vs. precontemplation: adjusted odds ratio (AOR) = 2.10, 95% confidence interval (CI), 1.36–3.25, P = 0.001; preparation vs. precontemplation: AOR = 1.83, 95% CI, 1.20–2.78, P = 0.005; contemplation vs. preparation: AOR = 1.15, 95% CI, 0.75–1.77, P = 0.52] and from 59% to 78% across confidence (medium vs. low: AOR = 1.91, 95% CI, 1.19–3.07, P = 0.007; high vs. low: AOR = 2.62, 95% CI, 1.68–4.10, P < 0.001; medium vs. high: AOR = 0.73, 95% CI, 0.48–1.11, P = 0.14).

Conclusions: Among disproportionately burdened community smokers, most hold favorable attitudes toward precision smoking treatment. Individuals with lower motivation and confidence to quit may benefit from additional intervention to engage with precision smoking treatment.

Impact: Predominantly favorable attitudes toward precision smoking treatment suggest promise for future research testing their effectiveness and implementation.