Non-typhoidal Salmonella (NTS) and thermotolerant Campylobacter remain leading causes of bacterial gastroenteritis worldwide, with a disproportionate burden in low- and middle-income regions. This updated review synthesizes current evidence on their epidemiology, antimicrobial resistance (AMR) dynamics, and the role of genomic epidemiology within a One Health framework. The global expansion of multidrug-resistant clones, driven largely by antimicrobial use in agriculture, increasingly compromises therapeutic options. Advances in whole-genome sequencing (WGS) have enhanced outbreak detection, source attribution, and tracking of AMR gene transmission across human, animal, and environmental reservoirs. Recent large-scale genomic analyses further clarify the temporal evolution and international dissemination of high-risk lineages. We argue that effective mitigation requires coordinated genomic surveillance, strengthened antimicrobial stewardship, and targeted interventions across the food chain. Implementing genomics-informed, cross-sectoral strategies under the One Health paradigm is essential to reduce disease burden and contain the spread of resistance.