To improve the understanding of the reactions and mechanisms occurring during the leaching of sulfide ores at high temperatures a range of advanced characterisation and sensing tools have been combined to provide a sophisticated and powerful methodology to examine sulfide leaching systems. These include advanced electrochemical methods, surface chemistry and materials characterisation techniques such as synchrotron X-Ray Absorption Spectroscopy (XAS), X-Ray Photoelectron Spectroscopy (XPS), Scanning Electrochemical Microscopy (SECM), and in situ X-ray diffraction (XRD), together with new robust solid state chemical sensors for in situ real time monitoring of key aqueous chemical parameters. The methodology was employed to investigate various sulfide mineral leaching processes. For example, oxidation of arsenopyrite at elevated temperature involves complicated multiple reactions and the process is strongly influenced by the solution conditions, component speciation and mineralogy. The methodology was used to study this system both ex situ and in situ to gain a detailed understanding of the complex chemical reaction mechanisms operating. These mechanisms are discussed in terms of the observed leaching efficiency. The application of this methodology enables complex sulfide leaching systems to be understood more fully such that process efficiency can be improved.