Problem-solving skills training (PSST) has a demonstrated potential to improve psychosocial well-being for parents of children with chronic health conditions (CHCs), but such evidence has not been fully systematically synthesized. To evaluate the associations of PSST with parental, pediatric, and family psychosocial outcomes. Six English-language databases (PubMed, Embase, CINAHL, PsycINFO, Web of Science, and Cochrane Library), 3 Chinese-language databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang), gray literature, and references were searched from inception to April 30, 2023. Randomized clinical trials (RCTs) that performed PSST for parents of children with CHCs and reported at least 1 parental, pediatric, or family psychosocial outcome were included. Study selection, data extraction, and quality assessment were conducted independently by 2 reviewers. Data were pooled for meta-analysis using the standardized mean difference (SMD) by the inverse variance method or a random-effects model. Subgroup analyses of children- and intervention-level characteristics were conducted. The psychosocial outcomes of the parents, their children, and their families, such as problem-solving skills, negative affectivity, quality of life (QOL), and family adaptation. The systematic review included 23 RCTs involving 3141 parents, and 21 of these trials were eligible for meta-analysis. There was a significant association between PSST and improvements in parental outcomes, including problem-solving skills (SMD, 0.43; 95% CI, 0.27-0.58), depression (SMD, -0.45; 95% CI, -0.66 to -0.23), distress (SMD, -0.61; 95% CI, -0.81 to -0.40), posttraumatic stress (SMD -0.39; 95% CI, -0.48 to -0.31), parenting stress (SMD, -0.62; 95% CI, -1.05 to -0.19), and QOL (SMD, 0.45; 95% CI, 0.15-0.74). For children, PSST was associated with better QOL (SMD, 0.76; 95% CI, 0.04-1.47) and fewer mental problems (SMD, -0.51; 95% CI, -0.68 to -0.34), as well as with less parent-child conflict (SMD, -0.38; 95% CI, -0.60 to -0.16). Subgroup analysis showed that PSST was more efficient for parents of children aged 10 years or younger or who were newly diagnosed with a CHC. Significant improvements in most outcomes were associated with PSST delivered online. These findings suggest that PSST for parents of children with CHCs may improve the psychosocial well-being of the parents, their children, and their families. Further high-quality RCTs with longer follow-up times and that explore physical and clinical outcomes are encouraged to generate adequate evidence.