Inside the nucleus of an intact cell, DNA is folded around histone proteins into nucleosomes and compacted into a multi-layered three-dimensional chromatin network, where nanometre-scale spacing between nucleosomes locally modulates DNA template access and regulates genome function. Observing nucleosome proximity in real time in live cells has been challenging due to its scale being below the diffraction limit of optical microscopy, even with advances in super-resolution imaging. To address this, we employ a combination of complementary quantitative imaging technologies: fluorescence lifetime and anisotropy imaging microscopy (FLIM and FAIM) of Förster resonance energy transfer (FRET) between fluorescently labelled histones to monitor nucleosome proximity, and fluorescence fluctuation spectroscopy (FFS) of inert fluorescent tracers to report chromatin accessibility at sub-micron scales. Here, we present our latest findings on live-cell chromatin network structure and accessibility, demonstrating how these orthogonal approaches together provide a detailed, dynamic picture of chromatin compaction versus functional access, offering new insights into the regulation of genome function in living cells.