In most cases, the decision to invest in a new airport is not simple, mainly because of the complications in the planning process, the amount of capital that needs to be invested before the establishment of the business, and the number of stakeholders involved in the decision. The decision process is more complicated in restricted economic and financing conditions, where the performance of the business plan is strongly related to regional development prospects and future airport business outputs in the medium and long term. This paper provides an evaluation methodology approach to support decisions on airport development projects. The proposed methodology provides an evaluation framework based on a combination of an ex ante assessment analysis, considering the airport’s economic impact and its contribution to a specific regional economy. The Input–Output (IO) analysis framework is used to determine the economic footprint of the airport development. A series of key performance indicators (KPIs) are introduced to review the project performance in a given economic system. The case study is examined, focussing on a new airport at Heraklion in Crete (in the Kasteli valley), one of the most attractive tourist destinations in the southeast Mediterranean. Conventional wisdom is to present a systematic approach appropriate to relevant projects, providing essential tools that support decisions at the level of strategic planning. The approach is essential to provide key messages to national governments, decision makers, and stakeholders on the contribution of an airport investment to regional economic development and its contribution to the business ecosystem in the post-COVID-19 era.