Soil contamination by heavy metals (HMs) is an important eco-environmental problem in China. It is essential to understand the mechanisms of HMs interacting with solid-phased fractions of soil for effective control and remediation of HMs polluted soils. Due to the complexity and heterogeneity of soil as well as the varied sizes of soil particles ranging from millimeter to nanometer, microsites with different micro-structures and surface properties control the speciation, transformation and bioavailability of HMs. Therefore, it is of great importance to deeply understand the microscale interaction mechanisms of HMs within soil microsites in order to effectively predict and control environmental behaviors of HMs in soils. Synchrotron-based microprobe and scanning transmission X-ray microscopy (STXM), and nano-scale secondary ion mass spectrometry (NanoSIMS), with micro- and nano- scale spatial resolutions, provide a unique platform to investigate the microscale interaction mechanisms of HMs within soil microsites at environmental meaningful spatial scales. This review first gives a brief overview of the birth and development of environmental soil chemistry (ESC) of HMs, points out the bottleneck of the current development of ESC due to inherent complexity and heterogeneity of the soil, and summarizes the aforementioned three advanced techniques and their application in the investigation of microscale soil chemistry of HMs, and finally gives a perspective on future development in this field.