This white paper discusses CRISPR-Cas9 screening as a method to enhance drug discovery processes. It outlines the capabilities of functional genomic screening, emphasizing the ability to conduct parallel genetic perturbations across numerous genes. The document details the methodology involved in CRISPR-Cas9 screening, including the creation of genomic perturbations, measurement of phenotypic responses, and statistical analysis to establish relationships between gene disruptions and phenotypes. It explains the different approaches to CRISPR screening, such as pooled and arrayed screening, and their respective advantages and limitations. The paper also describes complex model applications, including 3D models and in vivo studies, which provide relevant clinical context. Additionally, considerations for selecting the appropriate CRISPR screening format based on model type, library, technology, treatment, and readouts are discussed. Overall, the white paper presents CRISPR-Cas9 screening as a versatile tool in advancing drug discovery by identifying drug targets and understanding gene interactions.