Spatial profiling, through single-cell gene-level expression data paired with cell localization, offers unprecedented biologic insights within the intact spatial context of cells in healthy and diseased tissue, adding a novel dimension to data interpretation. This review summarizes recent developments in this field, its application to allergy and inflammation, and recent single-cell resolution platforms designed for spatial transcriptomics with a focus on data processing and analyses for efficient biologic interpretation of data. By preserving spatial context, these technologies provide critical insights into tissue architecture and cellular interactions that are unattainable with traditional transcriptomics methods, such as revealing localized inflammatory cell network in atopic dermatitis and T-cell interactions in the lung in chronic obstructive pulmonary disease. Spatial profiling offers opportunities for discovering novel biomarkers, defining compartmentalization of immune responses within tissues and individual diseases, and accelerating novel discoveries toward a greater understanding of fundamental disease mechanisms and, eventually, toward the development of future targeted therapies.