Cognitive processes play a role in decision making, which involves processing stimuli, memory of experiences and working memory. Cognitive processes involve the role of neurotransmitters that support physiological and executive processes. In decision making there is also a role for neurotransmitters such as dopamine, serotonin, noradrenaline and glutamate. This research was carried out using a molecular mechanism prediction approach using machine learning with protein-protein interactions from the GeneCards database followed by interactions using Cytoscape and enrichment analysis. The results of predictions of molecular mechanisms in decision making show that there are 21 genes encoding neurotransmitter, serotonin, intention process, prefrontal cortex, frontal asymmetry and decision making functions. Enrichment analysis and intersections between genes involved in the functions above show that HTR2A, SCL6A4 and COMT are genes that influence decision making. That biological process, cellular component and molecular function have three protein HTR2A, SLC6A4, COMT. The gene encoding the serotonin transporter (SLC6A4), the serotonin 2A receptor gene (HTR2A). The 5-HTT (SLC6A4) is mainly located in the pre-synaptic membrane of the raphe nuclei neurons, which innervate many areas of the brain involved in cognition, mood and behaviour and the relationship between decision-making and executive function is sensitive to genetic factors—particularly COMT provide support for the cross-task adaptation of executive functions to domain-general cognitive ability. The conclusion of the prediction results is that the serotonergic system within corticolimbic structures, HTT and HTR2A, with a few exceptions, is involved in various forms of decision making.