In children and adolescents, risky behaviours such as tobacco use may be addressed by developing life skills. In the field of tobacco prevention, the deployment of playful activities for the development of life skills has received little attention. This review describes the methods and results of tobacco prevention interventions using playful activities to develop life skills in children and preteens. A literature search was conducted in the PubMed, Web of Science and PsycInfo databases. Articles were included in the review based on the following five criteria: (1) the article totally or partially concerns a study of a tobacco prevention intervention; (2) the subjects were children and preteens aged between 6 and 12 years (with an average age within this age range or with an interval including all or part of this age range), from a general or specific population; (3) the intervention was a life skills development action or program; (4) playful activities were employed; (5) design, implementation, evaluation methods and/or results are available in the article. A total of 11 studies, composed of 9 interventions, were included in this systematic review. Most were carried out in school settings (n = 8/11) and involved teachers (n = 7/11). Web-based interventions (video games, mobile health games/websites and e-learning programs) were the playful activities most often used (n = 4/11). The majority of the interventions aimed to develop social skills such as the ability to resist pressure (n = 9/11). In this review, there were only four randomized controlled trial (n = 4/11). The evaluation was immediately after the RCTs. Among the measured outcome variables, knowledge (n = 8/11), attitudes (n = 5/11), intentions (n = 5/11), self-efficacy (n = 4/11) and skills (n = 3/11) were the most assessed. Only two of the studies reviewed here conducted a process evaluation (n = 2/11). This systematic review provides guidance for future youth smoking prevention interventions. Among these, a process evaluation is strongly suggested, as well as the use of appropriate variables and validated scales to assess the effectiveness of prevention programs. In addition, participatory research must allow for the design of adapted and relevant interventions, but also for the proper development of intervention research methodologies in health promotion.