QGIS: Use 'replace' expression for 2 characters in one field calculation

You need to use a nested replace() function such as

replace(replace('£10,000.00','£',''),',','')

You can nest as many replace() as you want.

You can do both replacements using a single function call:

1) using regex_replace, where you would look for the two characters of interest (inside square brackets):

regexp_replace("field_name",'[£,]','')

or 2) the map variant of replace, where the map is a series of key-value, the key being the string being searched for and the value being the replacement string

replace("field_name",map('£','',',',''))