<p>Cells have distinct molecular repertoires on their surfaces and unique intracellular biomolecular profiles that play pivotal roles in orchestrating a myriad of biological responses in the context of growth, development and disease. A persistent challenge in the deep exploration of these cues has been in our inability to effectively and precisely capture the temporal and spatial characteristics of living cells. In this Perspective, we delve into techniques for temporal and two- and three-dimensional spatial omics analyses and underscore how their harmonious fusion promises to unlock insights into the dynamics and diversity of individual cells within biological systems such as tissues and organoids. We then explore four-dimensional profiling, a nascent but promising frontier that adds a temporal (fourth-dimension) component to three-dimensional omics; highlight the advancements, challenges and gaps in the field; and discuss potential strategies for further technological development.</p>