Patient-derived organoids (PDOs) are revolutionizing cancer research, serving as invaluable models for tumor biology and therapeutic screening. The fidelity and applicability of these organoids are fundamentally shaped by the tissue dissociation techniques employed, namely mechanical dissociation and enzymatic digestion. This comprehensive review delves into the nuances of these two methods, scrutinizing their effects on solid tumor organoid properties, including stemness, heterogeneity, long-term culturing. We discuss the advantages and limitations of each technique, with a focus on their impact on tumor microenvironment preservation, their application in drug screening and cancer modeling. Moreover, we examine how recent technological breakthroughs have bolstered the efficiency and scalability of organoid production through these methods. Our analysis is designed to assist researchers in choosing the optimal tissue dissociation strategy for their research objectives and to fuel the evolution of organoid-based cancer models.