Fix the weakest link
Money comes from the one-dropper loop and the systems it unlocks. If output is slow, prioritize an upgrade that directly improves the active chain before buying unrelated options.
Unlock new generation methods
The official description says new ways to generate money unlock as you progress. Reaching a new method is often more valuable than making many small purchases in an old one.
Plan the next reset
Rebirth can make future runs faster. Keep enough momentum to reach its meaningful benefit rather than resetting automatically at the first opportunity.