Climate and atmospheric CO2 effects on the balance between C3 and C4 plants have received conflicting interpretations based on the analysis of carbon isotopic fractionation (δ13C) in sediments. But, climate and CO2 effects on the C3/C4 balance and δ13C signal are rarely addressed together. Here, we use a process-based model (BIOME4) to disentangle these effects. We simulated the vegetation response to climate and CO2 atmospheric concentration (pCO2) in two sites in which vegetation changed oppositely, with respect to C3 and C4 plants abundance, during the Last Glacial Maximum to Holocene transition. The C3/C4 balance and δ13C signal were primarily sensitive to temperature and CO2 atmospheric partial pressure. The simulated variations were in agreement with patterns observed in palaeorecords. Water limitation favoured C4 plants in case of large negative deviation in rainfall. Although a global parameter, pCO2 affected the δ13C signal differently from one site to the other because of its effects on the C3/C4 balance and on carbon isotopic fractionation in C3 and C4 plants. Simulated Plant functional types (PFT) also differed in their composition and response from one site to the other. The C3/C4 balance involved different competing C3 and C4 PFT, and not homogeneous C3 and C4 poles as often assumed. Process-based vegetation modelling emphasizes the need to account for multiple factors when a palaeo-δ13C signal is used to reconstruct the C3/C4 balance.