We characterized substance use patterns and co-occurring substance use disorders among active cocaine base paste (CBP) users in Santiago, Chile using data from respondent-driven sampling (RDS) in three areas of Metropolitan Santiago. Recruitment began with nine seeds, reaching 398 active CBP users (18% women; mean age 37.7 years), defined as persons consuming CBP at least twice per week in the last three months. Population proportions and uncertainty were estimated accounting for individuals’ social network and homophily. The median CBP age of initiation was 21 years, and the median number of years using CBP was 7 for women and 15 for men. The median days of use in the past month was 25 days, with a median of 56 doses per week. The proportion of monthly income spent on CBP was 65%. The prevalence of substance use disorders (SUDs) were: 98% for CBP, 67% for alcohol, 60% for marijuana, and 41% for cocaine hydrochloride. Heavy polydrug use patterns and co-occurring SUDs are frequent among active CBP users in the metropolitan area of Santiago. Traditional surveillance strategies may have underestimated polysubstance use and co-occurring SUDs in active CBP users. RDS proved to be a feasible methodology that could be effectively used for substance use surveillance among hard-to-reach populations.