The high share of PV energy requires greater system flexibility to address the increased demand/supply imbalance induced by the inherent intermittency and variability of the solar resource. In this work, we have developed a methodology to evaluate the margins for imbalance reduction and flexibility that can be achieved by advanced solar/wind forecasting and by strengthening the national transmission grid connecting the Italian market areas. To this end, for the forecasting of the day-ahead supply that should be provided by dispatchable generators, we developed three advanced load/PV/wind forecasting methodologies based on a chain or on the optimal mix of different forecasting techniques. We showed that, compared to the baseline forecast, there is a large margin for the imbalance/flexibility reduction: 60.3% for the imbalance and 47.5% for the flexibility requirement. In contrast, the TSO forecast leaves only a small margin to reduce the imbalance of the system through more accurate forecasts, while a larger reduction can be achieved by removing the grid constrains between market zones. Furthermore, we have applied the new forecasting methodologies to estimate the amount of imbalance volumes/costs/flexibility/overgenerations that could be achieved in the future according to the Italian RES generation targets, highlighting some critical issues related to high variable renewable energy share.