Background: Using meta-regression, this article aims at establishing the minimum change in BMI-standard deviation score (SDS) needed to improve lipid profiles and blood pressure in children and adolescents with obesity, to aid future trials and guidelines. Methods: Studies with participants involved in lifestyle interventions, aged 4-19 years, with a diagnosis of obesity according to defined BMI thresholds, were considered for inclusion in a large systematic review. Interventions had to report pre- and post-intervention (or mean change in) BMI-SDS, plus either systolic blood pressure (SBP), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and/or triglycerides (TGs). Random-effects meta-regression quantified the relationship between mean change in BMI-SDS and mean change in cardiovascular outcomes. Results: Seventy-one papers reported various cardiovascular measurements and mean change in BMI-SDS. Fifty-four, 59, 46, and 54 studies were analyzed, reporting a change in SBP, HDL, LDL, and TG, respectively. Reduction in mean BMI-SDS was significantly related to improvements in SBP, LDL, TG, and HDL (p < 0.05); BMI-SDS reductions of 1, 1.2, and 0.7 ensured a mean reduction of SBP, LDL, and TG, respectively, although an equivalent value for HDL improvement was indeterminate. Conclusion: Reductions in mean BMI-SDS of >1, >1.2, or >0.7 are likely to reduce SBP, LDL, and TG, respectively. Further studies are needed to clarify the optimal duration, intensity, and setting for interventions. Consistency is required regarding derived BMI values to facilitate future systematic reviews and meta-analyses.