Problem Gambling (PG) represents a serious problem for affected individuals, their families and society in general. Previous approaches to understanding PG have been confined to only a subset of the psychobiological factors influencing PG. We present a model that attempts to integrate potential causal factors across levels of organization, providing empirical evidence from the vast literature on PG and complimentary literatures in decision-making and addiction. The model posits that components are arranged systematically to bias decisions in favor of either immediately approaching or avoiding targets affording the opportunity for immediate reward. Dopamine, Testosterone and Endogenous Opioids favor immediate approach, while Serotonin and Cortisol favor inhibition. Glutamate is involved in associative learning between stimuli and promotes the approach response through its link to the DA reward system. GABA functions to monitor performance and curb impulsive decision-making. Finally, while very high levels of Norepinephrine can induce arousal to an extent that is detrimental to sound decision-making, the reactivity of the Norepinephrine system and its effects of Cortisol levels can shift the focus towards long-term consequences, thereby inhibiting impulsive decisions. Empirical evidence is provided showing the effects of each component on PG and decision-making across behavioural, neuropsychological, functional neuroimaging and genetic levels. Last, an effect size analysis of the growing pharmacotherapy literature is presented. It is hoped that this model will stimulate multi-level research to solidify our comprehension of biased decision-making in PG and suggest pharmacological and psychological approaches to treatment.