The scheme - the site's biggest-ever redevelopment - could involve an overhaul of the outpatient department and car parking, a new pharmacy unit, theatres to undertake surgical procedures and the creation of a 'link bridge' connecting Weston Park with the neighbouring Royal Hallamshire Hospital and Jessop maternity wing.
Medical bosses also want to spruce up the main building with fresh cladding to give it a more modern appearance.
Sheffield Teaching Hospitals' directors and governors have been briefed about the scheme, which forms part of the trust's estate strategy for the next three years.
But chiefs have emphasised that - as NHS budgets remain tight - finding the necessary funds will be challenging, and a full business case for the redevelopment has not yet been considered.
The revamp would come on top of a £6.7 million project to refurbish wards at Weston Park, which began in 2016. The areas - Ward 2 and Ward 3 - have new equipment, beds and furnishings, and have been designed to create as much clinical space as possible.
A refurbishment of the site’s assessment unit was carried out before work on the wards started. Single rooms have allowed patients to be checked discreetly, offering more privacy.
Dr David Throssell, medical director at Sheffield Teaching Hospitals, said: "Over recent years, we have made significant improvements to Weston Park Hospital's facilities and services to enhance patient care and experience.
"We have a long term strategy which we have been progressing and some of which has already been actioned such as fantastic ward refurbishments, which were also supported by our excellent charities, and a new state-of-the-art assessment unit.
"The remaining developments outlined in the strategy have not yet been considered as a full business case and, of course, in the current climate funding is a key consideration.
"Therefore we cannot say at this stage that all of the developments will be able to go forward in the short term, but we are continuing to explore every opportunity to make appropriate improvements where we can.”
Weston Park, which opened 47 years ago, is one of only four dedicated cancer hospitals in the country, and provides chemotherapy and radiotherapy to thousands of patients from across South Yorkshire and beyond.
However, hospital bosses have identified 'deficiencies'. There are several areas where demand far outstrips the available capacity, in particular the outpatient and chemotherapy day case units.
Changes to car parking would address the rising number of visitors to the site on Whitham Road, while new retail and restaurant services are proposed to generate more income. Waiting and consultation rooms could be refurbished, and it is hoped the offices and educational facilities will be improved too.
The hospital superseded the Sheffield National Centre for Radiotherapy when it opened in April 1970. In 1995 it was designated as a cancer centre because of its specialist facilities for complex conditions.