Microalgae-based wastewater treatment is an alternative to physico-chemical and bacteria-based technologies. Microalgae-based wastewater treatment showed enormous potential, not only exhibiting excellent pollutant removal efficiencies but also unlimited opportunities for resource recovery. Despite its promising future, the question of selecting autotrophy or heterotrophy regimes for optimal organic pollutant removal remains. This current work juxtaposes the performance of autotrophic and heterotrophic cultures in treating organic-rich wastewater to shed light on the unsolved puzzle. This review paper details the autotrophy and heterotrophy growth regimes for microalgae, as well as highlights the source of organic-rich wastewater and its characteristics. A clear comparison between both regimes was then discussed with recent references. Heterotrophic cultures showed better parameter removal performances, especially carbon-related and N-related compounds, while the removal of P-related compounds is considerably similar. Heterotrophic regimes also resulted in higher biomass yield with higher P content as compared to autotrophy. Despite their superiority, heterotrophic regimes continuously require additional carbon sources, posing a cost-related limitation. In contrast, autotrophic culture has an added value of carbon sequestration, making it beneficial for climate mitigation and lowering operational costs. Future research should concentrate on techno-economic and cost-benefit analyses to further refine the currently discussed topic.