DNA modification plays a pivotal role in regulating gene expression in cell development. As prevalent markers on DNA, 5-methylcytosine (5mC), N6-methyladenine (6mA), and N4-methylcytosine (4mC) can be recognized by specific methyltransferases, facilitating cellular defense and the versatile regulation of gene expression in eukaryotes and prokaryotes. Recent advances in DNA sequencing technology have permitted the positions of different modifications to be resolved at the genome-wide scale, which has led to the discovery of several novel insights into the complexity and functions of multiple methylations. In this review, we summarize differences in the various mapping approaches and discuss their pros and cons with respect to their relative read depths, speeds, and costs. We also discuss the development of future sequencing technologies and strategies for improving the detection resolution of current sequencing technologies. Lastly, we speculate on the potentially instrumental role that these sequencing technologies might play in future research.