There are basically only two ways of reaching Puerto Maldonado from Cusco. They are:

Bus to Puerto Maldonado

The road link between Cusco and Puerto Maldonado has improved considerably. Not long ago it would have taken 2 or 3 days to reach Puerto Maldonado by Bus , but now it can be done in less than 24 hours, or at least during the dry season. Travelling by land during the wet season is probably not recommended.

Fly to Puerto Maldonado

The quickest and simplest way to reach Puerto Maldonado from Cusco is by airplane which takes less than an hour. You can currently fly direct from Cusco and for a reasonable price too (often much less than $150 for a roundtrip). However,  air carriers and routes change quite a lot in Peru. If there’s no direct flight then you would have to go via Lima at considerably more expense. It is also usually much cheaper to book flights inside Peru than from the outside.