John is the son of Domingos deSouza and Elpiniki Papacostandinou a Greek national. Domingos is the son of A. B Desouza (Parra) and Rosa Viegas e Souza (Anjuna). John is the brother of Anthony, who works for an IT startup company in Silicon Valley; Francis, who was the President and CEO of IMLogic until it was sold to Symantec and is now their Vice President of Information Foundation Systems; Sophie, who works at IBM and Mario, who is a research associate at Stanford University Medical Center.

John, like his brother Francis, came to the US when he was 16 and attended MIT. "Having been born in Ethiopia and finishing high school in the United Arab Emirates it was a dream to be able to attend one of the top universities in the world. I can still remember the excitement on finding out that I had been accepted to MIT and, equally importantly, that I had received a full scholarship to attend. Having my brother at MIT eased my transition to the US and the pace and intensity of MIT has served me well throughout my career."

John de Souza has over a decade experience focusing on technology startups and technology investing. John's first startup experience was starting an instant messaging software company, Flash Communications, with his brother Francis. The company was purchased by Microsoft. He then joined some MIT friends to work at DESoFT, an brokerage technology startup, which was purchased by Merrill Lynch. John then co-founded a financial software company, Smartleaf, before joining Goldman Sachs to focus on investing in private technology companies. After five years of technology investing John decided to combine his skills and led an investment in MedHelp and took over as its President and CEO.