Pluripotency in embryonic stem cells (ESCs) is a highly dynamic process and exists as a continuum of pluripotent states including naive, formative, and primed state. The transition of pluripotency between different states is a key process in ESC fate decisions and is driven by signalling and transcriptional networks established by key kinases and transcription factors. To understand the key steps in ESC fate decisions, we have recently dissected the phased progression of pluripotency from naive towards primed state using a trans-omic approach. Through the comprehensive mapping of the proteome, phosphoproteome, transcriptome, and epigenome of ESCs transitioning from naive towards primed pluripotency, we find that rapid, acute, and widespread changes to the phosphoproteome precede ordered changes to the epigenome, transcriptome, and proteome. Computational reconstruction of signalling and transcriptional networks identifies key kinases, substrates, transcriptional factors, chromatin remodellers, and their downstream targets that together govern ESC fates through the continuum of pluripotent states.