New upgrade is unlocked when you choose them at least once during a run.

Powerups like critical hits or pets can only be upgraded once in the shop. If you have already unlocked the achievement of buying every item in shop then there is no more upgrades available.

If you are struggling with finishing even one run, I would suggest just get dragon at every boss upgrade and pick up HP and hit dmg reduction here and there until you can figure out other builds. The three dragon bosses each has a chance of giving you level 3 dragon with 240 dmg, if you do not see this upgrade , you can spend 2 coins to reroll the options