Complex subsurface contamination domains and limited efficacy of existing treatment approaches pose significant challenges to site remediation and underscore the need for technological innovation to develop cost-effective remedies. Here, we discuss opportunities for nanotechnology-enabled in situ remediation technologies to address soil and groundwater contamination. The discussion covers candidate nanomaterials, applications of nanomaterials to complement existing remediation approaches and address emerging contaminants, as well as the potential barriers for implementation and strategies and research needs to overcome these barriers. Promising nanomaterials in subsurface remediation include multi-functional nanocomposites for synergistic contaminant sequestration and degradation, selective adsorbents and catalysts, nano-tracers for subsurface contaminant delineation, and slow-release reagents enabled by stimuli-responsive nanomaterials. Limitations on mixing and transport of nanomaterials in the subsurface are severe constraints for in situ applications of these materials. Mixing enhancements are needed to overcome transport limitations in laminar flow environments. Reactive nanomaterials may be generated in situ to remediate contamination in low hydraulic conductivity zones. Overall, nano-enabled remediation technologies may improve remediation performance for a broad range of legacy and emerging contaminants. These technologies should continue to be developed and tested to discern theoretical hypotheses from feasible opportunities, and to establish realistic performance expectations for in situ remediation techniques using engineered nanomaterials alone or in combination with other technologies.