Antimicrobial resistance is a rigorous health issue around the world. Because of the short turn-around-time and broad pathogen spectrum, culture-independent metagenomic next-generation sequencing (mNGS) is a powerful and highly efficient tool for clinical pathogen detection. The increasing question is whether mNGS is practical in the prediction of antimicrobial susceptibility. This review summarizes the current mNGS-based antimicrobial susceptibility testing technologies. The critical determinants of mNGS-based antibacterial resistance prediction have been comprehensively analyzed, including antimicrobial resistance databases, sequence alignment tools, detection tools for genomic antimicrobial resistance determinants, as well as resistance prediction models. The clinical challenges for mNGS-based antibacterial resistance prediction have also been reviewed and discussed.