Human biology is highly complex and despite advances in technology development, we lack an understanding of how the many thousands of molecules and features of a cell make up a tissue. This can only be achieved through combining an array of advanced imaging-based techniques that simultaneously capture the breadth of spatial and temporal scales that make up a cell, tissue and organism. Massive untapped potential exists in developing domain-crossing technology and workflows to answer the critical discovery research questions and drive a step change in our understanding of health and disease. To address this challenge, our ambition is to combine novel imaging technologies, tools and integrated pipelines for multimodal interrogation of dynamic 3D functional human cell/tissue state. We will develop parallel instruments and tools capable of explaining genetic, biochemical and structural relationships in intact human tissues, both living and fixed. Through computationally spatially integrating, analysing and annotating these features and defining easy routes to share and analyse the data, we will provide means to test functional transition mechanisms in health and disease. These advances will enable mechanistic understanding of spatial signatures and dynamics that control tissue homeostasis and identify novel routes for therapeutic intervention.