Microalgae cultivation is a potential solution for renewable energy supply issues and environmental remediation; however, low CO2 absorption rates and volumetric productivities restrain commercial application of algal biotechnology. Mixotrophic and high-alkalinity/high-pH approaches for improving the productivity and cost-effectiveness were evaluated. Although mixotrophic cultivation of Chlamydomonas reinhardtii at low light exposure and high inoculum concentrations showed an improvement in biomass productivity (0.080±0.057 g/L·d in phototrophic experiments versus 0.44±0.163 g/L·d in mixotrophic experiments), values were not sufficient to improve performance of large scale microalgal technology. On the other hand, the high-alkalinity/high-pH approach showed a better performance in terms of lower use of resources and smaller equipment size reflected in three-fold less water requirements, twice the energy return on energy investment (EROI) and four-fold lower production costs (8.03 to 1.63 2013 US$/kg biomass). Economic and environmental results highlight the potential of high–alkalinity/high-pH systems in terms of productivity and cost-effectiveness of microalgal technology.