The misuse and over-prescription of antibiotics have contributed to the growing global threat of antimicrobial resistance (AMR), which undermines the efficacy of many antibiotics, including amoxicillin. AMR poses serious risks, such as increased mortality, prolonged hospital stays, and significant burdens on healthcare systems. In this study, we conducted a spatial analysis of amoxicillin resistance across 28 administrative units (Tehsils) of the Malakand region of Pakistan, a mountainous area in the Himalayan foothills where over 90% of the population resides in rural areas with limited access to healthcare. Hotspot analysis and Local Indicators of Spatial Autocorrelation (LISA) were used to identify local clusters of amoxicillin resistance. The central Tehsils of Wari, Lal Qilla, and Kabal were identified as significant hotspots and clusters of resistance. Linear regression explored associations of amoxicillin resistance with potential contributing factors at the regional level. Further, Geographically Weighted Regression (GWR) indicated which of the Tehsils exhibited significant risk factors for amoxicillin resistance. Significant contributors to amoxicillin resistance were rural population portion and illiteracy rates (aged 10 years and above). The GWR analysis provided detailed insight into the geographic variation of these risk factors, highlighting specific Tehsils where interventions may be most needed. Our findings underscore the importance of spatial analysis in identifying geographic inequalities in amoxicillin resistance. These results can aid policymakers and healthcare planners in targeting high-risk areas for further investigation and evidence-based interventions to mitigate the growing AMR threat.