Academic spin-offs are increasingly recognized as key contributors to digital transformation, serving as bridges between university research and applied technological innovation. This paper investigates the role of academic spin-offs in Greece, focusing on nine ventures that operate in data-driven sectors such as smart health, AI-enhanced bioprinting, DevOps analytics, autonomous mobility, environmental monitoring, and logistics optimization. Through a case study methodology supported by national-level trend analysis, we explore how these spin-offs leverage Big Data, artificial intelligence, and cloud infrastructure to commercialize research outputs and align with national innovation objectives. The study also considers the influence of the 2021 legislative framework on spin-off growth and identifies ongoing structural challenges, offering practical insights and policy recommendations to strengthen academic entrepreneurship in the digital economy.