Note that since Fennel 1.5.0, you can also just use set:

(local tbl [1 [:a :b :c] 3])
(set (. tbl 2 3) :e)

Note that you give multiple indices to perform nested sets.

(set tbl.2.3) doesn't work for the same reason it doesn't work in Lua, that 2 and 3 would be string keys.