Hand, Foot, and Mouth Disease (HFMD) is a infectious disease characterized by ulcers and blisters, primarily affecting children. The objective of this quantitative study is to identify areas with the highest HFMD cases (hotspot areas) in Jakarta in 2024 and to classify areas (districts) based on the number of HFMD cases and variables associated with the disease. The analysis employs the Local Indicator of Spatial Association (LISA) Cluster Map to detect spatial hotspots and K-Means Clustering to group districts by HFMD cases and related variables. LISA is a univariate method for detecting hotspots based on the local Moran’s Index that measures spatial dependence, whereas K-Means Clustering is a multivariate method for grouping individuals based on multiple variables. This study uses data from official government sources, including the number of HFMD cases, population density, average number of students per kindergarten, and average number of students per elementary school. The results of this study show that the LISA clustering reveals Kalideres and Cengkareng as High-High (H-H) clusters, while Tanah Abang, Menteng, and Senen form Low-Low (L-L) clusters. Makasar is classified as a Low-High (L-H) cluster. In contrast, the K-Means clustering groups districts into four clusters based on HFMD cases and related demographic factors, sorted in ascending order of HFMD cases. Areas with the lowest HFMD cases tend to have a moderate population density and fewer average number of students per kindergarten, while areas with the highest cases tend to have a lower population density but a higher average number of students per kindergarten. Areas classified as high cases HFMD by both methods, such as Cengkareng, should be prioritized for intervention. Cengkareng represents a district with the highest HFMD cases despite having a relatively low population density, along with a high average number of students per kindergarten and per elementary school.