This chapter deals with the corporate investment decision-making strategies amid the transformative landscape of Industry 5.0 and system-level Digital Twins Twinning. Through the lens of Strategic Foresight (SF) and Real Options (RO), the chapter both identifies a methodological gap in the literature regarding the integration of ROs and SF and underscores the potential synergy between these two fields. It is suggested that ROs can adeptly address numerical uncertainties in resource exploitation business cases, while SF serves as a valuable qualitative exploration tool under structural or radical uncertainty. A high-level, integrated decision framework is drafted, and its applicability is discussed within the Industry 5.0 context of system-level Digital Twins.