The biochemical composition of microalgae is significantly altered by growth conditions, thereby necessitating cultivation in precise culture conditions to synthesize biomass as feedstock for production of high-value compounds and biofuels. Nonetheless, culture conditions which promote rapid microalgal growth yields biomass with low concentrations of target metabolites (carotenoids, lipids, carbohydrates, etc.). Conversely, stress conditions introduced to trigger the induction of desired compounds in microalgal cells have an inhibitory effect on growth. Due to the contrasting conditions required for biomass production and accumulation of target compounds, a trade-off is often necessitated to increase the overall product yields. Two-stage microalgae cultivation, wherein biomass growth and product accumulation are separated into two discrete steps, has been identified as a viable approach to enhance the productivity of target compounds. In the first stage, optimal growth conditions are provided to achieve high biomass productivities, followed by exposure of cells to stress conditions for accumulation of target metabolites in the second stage. Microalgae cultivation systems constitute of open or closed reactors operated in batch, fed-batch, continuous or semi-continuous modes; under photoautotrophic, heterotrophic or mixotrophic metabolisms. In two-stage cultivation, two such configurations are integrated sequentially to exploit the inherent advantages of distinct cultivation systems. Nonetheless, the design of two-stage systems should be application specific as optimal culture conditions of each stage are reliant on the microalgal strain and the desired output. The present review provides an in-depth analysis on engineering approaches used for two-stage microalgae cultivation from an application-specific perspective, inclusive of discussion on techno-economic assessment and life cycle analysis of systems used for the biosynthesis of valuable compounds, generation of biofuel feedstock and wastewater bioremediation.