Purpose <p>This systematic review and meta-analysis investigates the diagnostic utility of [¹⁸F]Fluorodeoxyglucose (FDG) and Fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) in Crohn’s disease (CD).</p> Methods <p>A comprehensive literature search of Scopus, PubMed, and Web of Science up to April 1, 2025 was performed. Pooled detection rates, sensitivity, specificity, average maximum standardized uptake value (SUVmax), and biomarker correlations were assessed using Stata software.</p> Results <p>This systematic review evaluates 20 studies (547 patients, 1935 bowel segments) comparing [¹⁸F]FDG and FAPI PET tracers in CD. Seven [¹⁸F]FDG PET studies (247 patients, 872 segments) demonstrated pooled sensitivity, specificity, and accuracy of 76%, 81%, and 85%. Overall detection rate for CD inflammation was 89%, with SUVmax weighted mean difference (WMD) of 2.9 between inflammatory and non-inflammatory segments (<i>p</i> = 0.0001). [¹⁸F]FDG SUVmax correlated strongly with CRP (rho = 0.67, <i>p</i> = 0.001). Four FAPI PET studies (50 patients, 211 segments) showed 92%, 93%, and 96% sensitivity, specificity, and accuracy. Overall, the detection rate for CD fibrosis was 99%, and the WMD in SUVmax between fibrotic and non-fibrotic CD is 7 (<i>p</i> = 0.00001). FAPI SUVmax correlated strongly with histologic fibrosis grading (rho = 0.74, <i>p</i> = 0.0001). Indirect comparisons revealed FAPI’s diagnostic effectiveness was twofold greater than FDG (<i>p</i> = 0.03), and has higher overall SUVmax with WMD of 1.3 (<i>p</i> = 0.01).</p> Conclusion <p>Both PET tracers show promise, with [¹⁸F]FDG correlating with CD inflammation, and FAPI with CD fibrosis. FAPI PET imaging demonstrated greater accuracy and higher uptake metrics. Further research is needed to explore diagnostic and predictive utilities in larger studies.</p>