The copper, cobalt and nickel ores are still currently mined in the world. Its complex mineralogy creates extraction challenges by means of conventional metallurgical methods. Meanwhile, dealing with mesophilic strains in leaching process requires a compromise between solid loading and microbiota activity and growth. That is why, the influence of solid loading with fine or coarse particulates, the cell disturbance during the metal–microbes interactions depending upon the influence of gangue nature as well as metallic ions concentration on bacterial tolerance and the chemical and biological pathways involved in bioleaching mechanism of complex ores are summarised in detail in this paper. The current trends in mechanism research and diverse discovered set of microbiota and bacterial population coupled with bacterial adaptation methods contribute to optimise and improve the metals leaching performance and knowledge. In addition, the different existing complex mineralogical structures elaborate a main indirect mechanism with two different transitory mechanisms, before metal is converted into metal sulphate as wealthily explained in this comprehensive review. More data for cost analysis concomitant with extraction efficiency of metals using mesophilic bioleaching process are needed. However, it does not mean that other options are excluded in order to set a bio-hydrometallurgical chain. In fact, to consider also the concentration and purification of the pregnant leaching solution via phase separation and solvent extraction will be helpful. This obeys to the idea of option trees, where possible options are then systematically gaged with respect to critical criteria.