Background: The main objective was to examine sexual assertiveness and sexual satisfaction in people who have sex under the influence of alcohol and drugs, considering the type of substance consumed, the frequency of consumption, gender, and sexual orientation. Methods: The sample consisted of 274 adults who had sexual relationships consuming substances. A questionnaire composed of sociodemographic, sexual history and substance use items, the Sexual Assertiveness Scale and the Global Measure of Sexual Satisfaction were administered. Results: Gender differences were found in sexual assertiveness and in the frequency of substance use. Women reported greater sexual assertiveness and greater alcohol consumption. Men reported greater consumption of different types of substances. Furthermore, bisexual participants showed greater assertiveness and STI prevention. Homosexual participants reported a higher frequency of the consumption of poppers, mephedrone, and GBL/GHB. Sexual assertiveness was associated with sexual satisfaction. Greater consumption of some types of substances was related to sexual assertiveness, STI prevention, and sexual satisfaction. Conclusions: The association found between sexual assertiveness and sexual satisfaction in a specific context of substance use in sexual relationships corroborates the important role that these psychosexual variables have in sexual health, in view of the frequency and type of drug consumed, gender, and sexual orientation.