Overview of a multi-modal approach to the study of neutrophils in cancer and beyond. Intravital microscopy is a powerful tool to characterize in vivo cell biology of neutrophil trafficking and function in tissues. Ex vivo assays like laminar flow chambers, microfluidics, and in vitro functional assays, together with emerging technologies of organoids and organs-on-a-chip, are used to understand the dynamic functions of human neutrophils. Deep characterization of neutrophil heterogeneity, plasticity, and functional regulation are facilitated by high-dimensional transcriptomic, epigenomic, and proteomic methodologies, which can also enable a systems biology approach to the study of neutrophils in vivo.