Most of the municipal solid waste (MSW) generated in the Latin America (LATAM) region is currently disposed of in landfills and dumpsites, which results in many negative environmental impacts. Mechanical biological treatment (MBT) is a strategy that combines the mechanical separation of recoverable materials with the biological stabilization of organic matter. MBT plants have proven to be a good alternative for the management of MSW and have been successfully implemented in developed countries for more than 30 years. However, the efficient introduction of these facilities in developing countries, such as those in the LATAM region, requires further feasibility studies. Therefore, this mini review seeks to offer significant insights into the main challenges that must be overcome to facilitate the implementation and operation of MBT plants, considering the unique technological, sociocultural, economic and political context of the LATAM region, through a comparison of the reported experiences of MBT plants in more developed countries with those in the LATAM region. The analysis herein indicates that key actions for the successful operation of MBT plants in the LATAM region include both the implementation of source separation as well as selective collection practices. Moreover, this work shows that other factors, like the establishment of valorization markets with safe working conditions for informal collectors, the development of intermunicipal cooperation schemes and the enforcement of strong regulatory frameworks for waste disposal specifications, are important contextual factors that have allowed the efficient operation of MBT plants in developed countries. Although the implementation of many of these practices will be challenging, such measures are necessary to increase the sustainability of MSW treatment practices in the LATAM region.