Geographic Information Systems have grown over time to become an integrative tool in public health, providing an effective way of bringing spatial data together in assessing some of the complex health challenges. The aim of this systematic review is to delve into the application of GIS in addressing public health challenges and identify the knowledge gaps on the existing limitations on the way to harnessing new technologies in GIS and maximizing their impact on population health. In 45 articles reviewed, the authors found evidence that GIS have been essential in the field of public health. Most studies explored their use in disease surveillance and outbreak response, especially in the tracking of patterns of disease. Others discussed how GIS can be used in health disparity research for visualizing geographical patterning of health inequities and for revealing ways to implement interventions that would reduce inequities. Very few of them reviewed applications in health service planning and resource allocation, pointing to potential means of optimizing the geographical distribution of healthcare resources and increasing access to underserved populations. Finally, the authors consider how GIS can help to create comprehensive health profiles of communities by providing insights into health disparities. Our study provides an overview for future research on this topic and discusses the progress and the continued challenges of the field of public health GIS with respect to data quality, capacity building, and ethical and community considerations in order that its full potential for creating a healthier, more equitable world can be met.