Whether caffeine (CAF) increases fat metabolism remains debatable. Using systematic review coupled with meta-analysis, our aim was to determine effects of CAF on fat metabolism and the relevant factors moderating this effect. Electronic databases PubMed, SPORTDiscus, and Web of Science were searched using the following string: CAF AND (fat OR lipid) AND (metabolism OR oxidation). A meta-analytic approach aggregated data from 94 studies examining CAF’s effect on fat metabolism assessed by different biomarkers. The overall effect size (ES) was 0.39 (95% confidence interval [CI] [0.30, 0.47], p < .001), indicating a small effect of CAF to increase fat metabolism; however, ES was significantly higher (p < .001) based on blood biomarkers (e.g., free fatty acids, glycerol) (ES = 0.55, 95% CI [0.43, 0.67]) versus expired gas analysis (respiratory exchange ratio, calculated fat oxidation) (ES = 0.26, 95% CI [0.16, 0.37]), although both were greater than zero. Fat metabolism increased to a greater extent (p = .02) during rest (ES = 0.51, 95% CI [0.41, 0.62]) versus exercise (ES = 0.35, 95% CI [0.26, 0.44]) across all studies, although ES was not different for studies reporting both conditions (ES = 0.49 and 0.44, respectively). There were no subgroup differences based on participants’ fitness level, sex, or CAF dosage. CAF ingestion increases fat metabolism but is more consistent with blood biomarkers versus whole-body gas exchange measures. CAF has a small effect during rest across all studies, although similar to exercise when compared within the same study. CAF dosage did not moderate this effect.