Antimicrobial resistance (AMR) presents a critical challenge in clinical settings, particularly among pediatric patients with life-threatening conditions such as sepsis, meningitis, and neonatal infections. The increasing prevalence of multi- and pan-resistant pathogens is strongly associated with adverse clinical outcomes. Recent technological advances in sequencing methods, including metagenomic next-generation sequencing (mNGS), Oxford Nanopore Technologies (ONT), and targeted sequencing (TS), have significantly enhanced the detection of both pathogens and their associated resistance genes. However, discrepancies between resistance gene detection and antimicrobial susceptibility testing (AST) often hinder the direct clinical application of sequencing results. These inconsistencies may arise from factors such as genetic mutations or variants in resistance genes, differences in the phenotypic expression of resistance, and the influence of environmental conditions on resistance levels, which can lead to variations in the observed resistance patterns. Machine learning (ML) provides a promising solution by integrating large-scale resistance data with sequencing outcomes, enabling more accurate predictions of pathogen drug susceptibility. This review explores the application of sequencing technologies and ML in the context of pediatric infections, with a focus on their potential to track the evolution of resistance genes and predict antibiotic susceptibility. The goal of this review is to promote the incorporation of ML-based predictions into clinical practice, thereby improving the management of AMR in pediatric populations.