He is a General Partner at the venture capital firm of DCVC in Palo Alto, California, and is a board member and seed investor in a number of life sciences companies.

Pontin engaged in what The Boston Globe has described as a "strategic overhaul" of Technology Review, whose goal is to make the magazine into a largely electronic publishing company.

AdWeek commented that "Pontin and MIT Technology Review could set the standard for the transition to a digital future for legacy media.

[17][18] In 2015, he cofounded MIT Solve[19] the institute's open innovation platform, which deploys capital and other resources towards solutions to grand challenges.

[21][22][23][24] In 2019, with CEO Neil Dhawan, he cofounded Totus Medicines, a chemical biology company whose drug discovery platform uses structure-based design, combinatorial chemistry, and automated biophysics to rapidly identify oncology therapies.