Here we describe the full wetlab protocol for scNMT-seq (single-cell nucleosome position, methylome and transcriptome sequencing), a plate-based single-cell multi-omic method.In scNMT-seq, a GpC methyltransferase is used to label non-nucleosome bound DNA thus encoding chromatin accessiblity information within the genomic DNA. Bisulfite conversion is then used to discriminate the two chromatin states which can be read from GpC dinucleotide positions. Endogenous DNA methylation is read from the CpG positions of the same molecules and gene expression data is obtained by capturing poly-A RNA on magnetic beads and pysically separating before the gDNA is bisulfite converted. This mRNA on beads is pocessed using Smart-seq2. The protocol is carried out in 96w plates and typically takes 3-4 days to complete.