Tirzepatide has become a treatment option for weight management, with increasing interest in its effects on skeletal muscle. This systematic review evaluated the impact of tirzepatide on skeletal muscle mass and lean body composition in adults. A structured search of four major databases was conducted up to June 26, 2025, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The included studies were randomized clinical trials that assessed skeletal muscle or lean mass using validated imaging methods in adults treated with tirzepatide. The available evidence suggests that treatment is associated with reductions in fat mass while maintaining the relative preservation of lean mass. Indicators of muscle composition remained stable or showed signs of improvement. These findings support the potential of tirzepatide to improve overall body composition without significantly compromising skeletal muscle. Further research is needed to confirm these results and explore their functional significance over time.