Here are some options for scenic trips between Wengen and Varenna, with an overnight in a nice place one the way. You can use this rail map of Switzerland to trace them. Note that dashed lines on the map indicate tunnels. Every journey, no matter which route you use, starts with the transfer from Wengen down to Interlaken Ost, so I have left that part out of each route description to simplify. You will have to add about an hour to the times for that transfer.
https://www.swissrailways.com/sites/default/files/sts-gb-m-15-web_vorlage_0.pdf
Train route via Luzern and Locarno, using the Treno Gottardo:
Start with the Golden Pass scenic train heading east from Interlaken over the Brunig Pass to Luzern. Journey time 1 hour 50 minutes, no train changes. At Luzern, transfer to the Treno Gottardo regional train (IR26) which goes directly to Locarno (no changes) on the old Gotthard Pass route. Note that this route does have a short tunnel near the top, but you will see plenty of scenery before and after the tunnel—-some of it multiple times as the train switchbacks up the mountainside. This train departs Luzern every two hours; you should be able to catch the 13:18 departure with an early start from Wengen.
https://www.myswitzerland.com/en-us/experiences/treno-gottardo/
https://www.swissholidayco.com/Scenic-Holidays/Treno-Gottardo
The journey to Locarno is 3 hours. This is a pretty lakeside town with hotels right on the lake just a block or two from the train station. Overnight there.
Next day, take the train heading toward Milan but get off at Monza and transfer to the regional train to Varenna. Total time for this trip 3 hours, including the transfer time at Monza.
An alternative if you prefer a boat ride would be to leave the train from Locarno at Como San Giovanni on lake Como, and take a ferry up the lake to Varenna. But this would add several hours to the travel time.
Train route using the Bernina Pass route:
This route was mentioned by RailRider above. You travel from Interlaken to an alpine village along the Bernina Pass route (I suggest Pontresina), where you overnight. The following day board either the named Bernina Express train with its panoramic cars, or one of the regular regional trains that runs hourly over the same tracks, with the same scenery. Either one will take you tinTirano on the Swiss-Italy border. Change there to an Italian train directly to Varenna.
https://www.rhb.ch/en/panoramic-trains/bernina-express
Travel time for this option: Interlaken to Pontresina via Zurich and Chur, 5.5 to 6 hours, with 3-4 changes on the way. Overnight Pontresina. Journey to Varenna-Esino the following day is 3.5 hours, with a single change at Tirano.
Train, boat and bus route via Luzern and Lugano:
This route takes you to Lugano, where you can board a bus to Menaggio on Lake Como, directly across the lake from Varenna. That is a short ferry ride ( about 20 minutes as I recall. The bus goes along Lago Lugano but we have never done it so I don’t know what the scenery is like, or how long the bus takes.
Your options for getting to Lugano from Luzern include the fast route using the deep Gotthard Basistunnel (4 hours total from Interlaken to Lugano, with a single change in Luzern), the scenic route using the Gotthard Panorama Express (boat from Luzern to Flüelen and train over the Gotthard Pass route from there, or a combination of Treno Gottardo and regional trains to reach Lugano instead of Locarno. I did not figure out the timing on the various options but here is more information on the Gotthard Panorama Express (boat plus train):
https://www.myswitzerland.com/en-us/experiences/gotthard-panorama-express/