In the March quarter, growth in Asia's third-largest economy skidded to a nine-year low of 5.3 percent even as inflation rose to nearly 7.6 percent in May.
Wide current account and fiscal deficits have battered investor sentiment and recently sent the rupee tumbling to a record low, raising the spectre of a balance of payment crisis like the one India faced in 1991.
Known as a Congress trouble-shooter, Mukherjee has been thwarted by a fractious ruling coalition from pushing through reforms, and it's not clear whether his successor would get better results.
In the absence of an obvious successor, talk in New Delhi also suggests Prime Minister Manmohan Singh could take the finance portfolio, possibly on an interim basis.
Singh was finance minister during India's 1991 crisis, pushing through reforms that unleashed two decades of faster growth.
If he does opt for a full-time finance minister, there are several names doing the rounds.
Following are profiles of some of the probable candidates that Prime Minister Manmohan Singh and his party chief Sonia Gandhi may look to replace Mukherjee.