The Forma Urbis Romae (F.U.) was a 3rd-century-AD monumental map of ancient Rome consisting of 151 rectangular marble slabs. Several efforts have been made to reconstruct it from its current incomplete and fragmentary condition. In this paper, we explore the potential of an archaeometric approach to serve this purpose. Almost a hundred F.U. fragments have been characterized, particularly focusing on cathodoluminescence (CL) microscopy and stable isotopes (δ18O and δ13C). Different statistical methods have been used to quantify the similarity between samples. The central assumption is that samples from a given slab share similar CL colors and isotopic ratios. The assumption has been verified for samples from single fragments and then it has been used to check ten debated reconstruction hypotheses. The measured isotopic ratios confirm the Proconnesian nature of the F.U. marble, except for a fragment. Beyond provenance, the results cast doubts on four out of the ten checked reconstruction hypotheses and support the other six. The reconstruction of the F.U. remains a fascinating challenge, and both isotopic and CL analyses have demonstrated their potential to tackle it. Further research could extend the presented methodology to a higher number of samples. The innovative use of CL to reconstruct a fragmented artwork could be applied to other projects.