Imaging based single cell systems biology analyses, i.e. Systems Microscopy, enable detailed mapping of cellular heterogeneity with spatial (cell population, single cell, subcellular) and temporal (minutes to days) resolution. Our emerging systems microscopy platform fuses live imaging with several complimentary strategies for multiplexed molecular analysis of fixed cell populations with subcellular resolution, feeding resulting data into deep learning-enabled image analysis and representation learning pipelines. Visual analytics tools, including virtual reality-based software, re-connect single cell images with their derived quantitative data to build an intuitive understanding of both cell heterogeneity and artificial intelligence models that interrogate it. This strategy underpins our fundamental research into cancer cell plasticity in the EMT and stemness spectra, as well as our work to develop liquid biopsy based precision diagnostics to enhance clinical decision-making. Related approaches are also applied to drive a 'CellaSense', a generalised drug lead discovery platform currently in development.