In recent years, esports (the competitive video game industry) have evolved significantly, revolutionizing not only the competitive scene but also the teams and their professional staff. Sports psychologists need to face with cognitive demands related to this activity primarily mental, to respond to the specific needs of the sector (e.g., high performance interventions). The aim of this study was to determine the relationship between cognitive performance in tests and the MOBA League of Legends (LOL) game scores. A group of 36 pure-genre LOL players was evaluated with behavioral tests of fluid intelligence, attentional control inhibition, working memory, cognitive flexibility, and decision making. Furthermore, their in-game performance (rank percentile, kills death assists, minions per minute, and vision score) was recorded during a complete season (approximately 1 year). Data was analyzed by means of correlation and multiple regression analysis. Results showed that cognitive flexibility was positively related to the “rank percentile” ( p < .001; R = .442; 95% CI [2.97, 74.76]). Besides, a positive relationship was found between decision making and the in-game performance variable “minions per minute” ( p = .009; R = .236; 95% CI [−8.46, 5.26]). These findings point that it is possible predict performance on specific variables, in esports with high cognitive impact throughout neuropsychological assessment. These results provide a starting point for research in the field of esports, sports psychology, and high-performance-oriented intervention.