Samuel Lewis began his business career in his family's company Empaques de Colon, where he became the general manager and president.

He is also the President of Calder International, a real estate company involved in housing development projects in Panama City.

At the same time, he has participated in business organizations such as the Industrial Guild of Panama; the Panamanian Association of Business Executives (APEDE in Spanish); the Panamanian Association of Exporters (APEX in Spanish); the Panamanian Chamber of Commerce; the American Chamber of Commerce and Industry of Panama (AMCHAM); The Young Presidents' Organization, and the Gabriel Lewis Galindo Foundation, dedicated to promoting education in Panama.

The latter state institution, wholly run by Panama since December 31, 1999, is responsible for the management of the waterway connecting the Atlantic and Pacific Oceans.

He resigned from it to contribute as an independent citizen to finding solutions to the serious social, political and moral problems facing the Panamanian nation.