In the current regional-scale study, the model DSSAT CROPGRO was applied in order to simulate the cultivation of industrial tomato and to estimate the green water (GW), blue water (BW), blue water requirement (BWR) and water footprint (WFP) through a dual-step approach (with and without full irrigation). Simulation covered a period of 30 years for three climate scenarios including a reference period and two future scenarios based on forecast global average temperature increases of 2 and 5 °C. The spatial patterns of indicators relating to the whole territory of Puglia region (Southern Italy), characterized by the high evaporative demand of the atmosphere, are discussed and analysed. Considering the climatic pattern, the analysis was developed for three areas (Northern, Central and Southern). Future scenarios affected all indicators significantly, particularly the Northern area, characterized by higher temperature and rainfall anomalies. Under the A5 scenario, compared with the baseline, this area was forecast to have a large increase of BW (+30%) and reduction in yield (−20%). As a consequence, the BWR and WFP were predicted to increase dramatically, up to 40 and >65%, respectively. On the other hand, Central and Southern areas, with lower anomalies of temperature and rainfall, were forecast to be less vulnerable to climate change. The distributed analysis performed could be important for water policy, allowing most efficient allocation of scarce water resources and concentrating them where the WFP is lowest, or in other words, water use efficiency is highest.