Vulnerability to compulsive drug use stems from dysregulated activity within the neural networks that underlie reward and executive functions. Empirical evidence suggests that a) attributing high motivational salience to drug-related stimuli leads to compulsive drug seeking and b) cognitive control deficits lead to compulsive drug taking. Noninvasive neuroimaging techniques enable brain activity monitoring during affective and cognitive processing and are paving the way to precision medicine for substance use disorders. Identifying robust neuromarkers of affective and cognitive dysregulation would allow clinicians to personalize treatments by targeting individual psychophysiological vulnerabilities. However, methodological choices have biased the field toward experimental paradigms that cannot optimally assess individual differences in the motivational salience of drug-related cues and in the ability to control drug-related decisions, choices which have hindered the identification of clinically relevant neuromarkers. Here, we show that once these shortcomings are amended, replicable neuromarkers of the tendency to attribute motivational salience to drug-related cues and the ability to control drug-related decisions emerge. While we use tobacco use disorder as a model, we also show that the methodological issues highlighted here are relevant to other disorders characterized by maladaptive appetitive behaviors.