During the SARS outbreak in 2003, Tambyah helped establish the NUH Division of Infectious Diseases, with Professor Dale Fisher and trainee Dr Louis Chai joined in December 2004.

[11] In June 2020, he became a president-elect of the International Society for Infectious Diseases, set to become the first Singaporean to hold the position and was expected to start his term in 2022.

[14] On 20 December 2022, Tambyah became the new President of the International Society of Infectious Diseases Executive Committee, replacing Alison Holmes who would currently serve as its immediate past-President.

[18] Tambyah started getting involved with the Singapore Democratic Party in 2010 and spoke as a guest speaker at the SDP rallies during the 2011 Singaporean general election.

[20] In 2015, he was fielded as a political candidate as part of the SDP team along with Dr Chee Soon Juan, Sidek Mallek and Chong Wai Fung and contested against PAP's Vivian Balakrishnan, Sim Ann, Liang Eng Hwa, and Christopher de Souza for the Holland–Bukit Timah Group Representation Constituency (GRC) in the 2015 Singaporean general election.

[21][22] On 30 June 2020, Tambyah was fielded as a SDP candidate against PAP's Liang for the Bukit Panjang Single Member Constituency during the 2020 Singaporean general election.