Several effective interventions have been developed for families with multiple problems (FMP), but knowledge is lacking as to which specific practice and program elements of these interventions deliver positive outcomes. The aim of this study is to assess the degree to which practice and program elements (contents of and structure in which care is provided) contribute to the effectiveness of interventions for FMP in general and for subgroups with child and/or parental psychiatric problems, intellectual disabilities, or substance use. We performed a quasi‐experimental study on the effectiveness of practice and program elements provided in attested FMP interventions. Using self‐report questionnaires, we measured primary (child's internalizing and externalizing problems) and secondary (parental stress and social contacts) outcomes at the beginning, end, and three months thereafter. By means of Latent Profile Analysis, we identified groups of families receiving similar combinations of practice elements (“profiles”), and we calculated propensity scores. Next, we assessed how practice element profiles and program elements affected improvement in outcomes, and whether these effects were moderated by subgroup characteristics. We found three practice element profiles (explorative/supportive, action‐oriented, and their combination), which were equally effective. Regarding program elements, effects were enhanced by more frequent telephone contact between visits and more frequent intervision. Effectiveness of practice and program elements varied for specific FMP subgroups. Variations in the content of care for FMP do not affect its effectiveness, but variations in the structure of the care do. This finding can help to further improve effective interventions.