Organoids have reshaped biomedical research by providing stem cell–derived model systems that capture key aspects of tissue organization, homeostasis, and disease. Their physiological relevance and adaptability have made them indispensable tools for studying development, regeneration, and tumor biology under controlled experimental conditions. This is particularly powerful in the human setting, where organoids offer an experimentally accessible alternative to in vivo studies that are ethically and practically unfeasible. Central to their success is the ability to apply diverse perturbation strategies, ranging from targeted genetic edits and pharmacological interventions to microenvironmental and biomechanical manipulations, that reveal the molecular logic of cellular and tissue function. In this review, we discuss the current landscape of organoid perturbation studies, highlighting methodological advances, representative applications, and what these efforts have taught us about cellular behavior in complex systems. By outlining methodological innovations and conceptual insights, we aim to establish a framework for using organoids not only as descriptive models but as predictive systems for probing and engineering human tissue behavior.