Mesenchymal stromal cell (MSC) therapy holds promising potential for the treatment of various pathological conditions associated with inflammatory processes. Despite encouraging outcomes in preclinical studies, the transition to successful clinical trials has been hindered by the absence of patient stratification criteria, the limited understanding of the in vivo mechanism of action, and the variability in MSC preparations. In this chapter, we address the major challenges in establishing a standardized manufacturing platform for MSC products and suggest new approaches to advance their clinical success.