The removal of heavy metals combined with biodiesel production by microalgae in a cost-effective way is a promising approach. Herein, we grew two green microalgal species, Chlorella sorokiniana and Scenedesmus acuminatus, in media contaminated with Cu2+ (3.2 ppm) or Zn2+ (65.4 ppm) to investigate their growth and full metabolic profile. Furthermore, to integrate the potential economic impact of biodiesel production with heavy metals removal efficiencies. Although acute exposure to heavy metals, on the other hand, reduced growth and increased removal efficiencies of Cu2+ (59.4, 98.1%) and Zn2+ (72.4, 98.2%) in C. sorokiniana and S. acuminatus, respectively. Besides, Cu2+ and Zn2+ increased primary metabolites, particularly lipids (49, 47% in S. acuminatus, 27, 26% in C. sorokiniana), with a significant induction in the unsaturation levels. Indicating that C. sorokiniana and S. acuminatus are excellent phycoremediators for industrial drainage and future sustainable algal-biofuels platform. Economic assessment of daily 1000-tonne biodiesel production from S. acuminatus grown on highly polluted wastewater via Na4SiO4 transesterification catalysis has all been assessed with an accuracy of ± 10% for the price of the diesel of US$ 1000/tonne and for the cost of the evaluated algal biomass of US$ 430/tonne. The daily 1000 T algal diesel business was viable, with a return on high investment (16.4%) and a payback period of 5 years. According to break-even and sensitivity analyses, the algal diesel cost that makes this business viable should be greater than US$ 147/barrel, while the biomass cost should not exceed US$ 462/tonne. Brent Crude Oil Spot exceeds US$ 95/barrel indicating promising prospects for algal fuel industrialization. Furthermore, the protein and amino acids-based waste biomass may serve as a sustainable biorefienry platform for various biofuel industries through biomass conversion technologies.