The COVID-19 pandemic has motivated the rapid development of numerous vaccines that have proven effective against SARS-CoV-2. Several of these successful vaccines are based on the adenoviral vector platform. The mass manufacturing of these vaccines poses great challenges, especially in the context of a pandemic where extremely large quantities must be produced quickly at an affordable cost. In this work, two baseline processes for the production of a COVID-19 adenoviral vector vaccine, B1 and P1, were designed, simulated and economically evaluated with the aid of the software SuperPro Designer. B1 used a batch cell culture viral production step, with a viral titer of 5 × 1010 viral particles (VP)/mL in both stainless-steel and disposable equipment. P1 used a perfusion cell culture viral production step, with a viral titer of 1 × 1012 VP/mL in exclusively disposable equipment. Both processes were sized to produce 400 M/yr vaccine doses. P1 led to a smaller cost per dose than B1 ($0.15 vs. $0.23) and required a much smaller capital investment ($126 M vs. $299 M). The media and facility-dependent expenses were found to be the main contributors to the operating cost. The results indicate that adenoviral vector vaccines can be practically manufactured at large scale and low cost.