The alien probe tool is required to fully explore the sewers. Enter the sewers from the manhole outside the news office. Use the alien probe to teleport to the other side. Go down the ladder then shoot the red valve to moderate the sewage flow. Go past it and turn the yellow valve to stop the flow completely. If you still have the sidequest “ManBearPig” active, the generator along the way is where you'll place the Defilibrator.
Go around the corner and head to the left. Pull the lever to remove the grate and for you to access Mr. Hankey's home. After a scene, this sidequest will become available. There's also a Chinpokomon right outside Mr. Hankey's house.
Continue to the left to find Amber. Climb up the ladder then go around the platform to the left. Turn the yellow valve to stop the flow then go down the ladder to reach Amber. Talk to her to rescue her and be added to your friend list.
Climb back up then head east this time. Turn the yellow valve along the way then use the catwalk to go around. Loot the grate in the middle for some items then continue to the right. Be careful of the waiting hobo. This is one of the seven homeless camps you need drive out as part of another sidequest.
Go further to the right and shoot the red valve along the way. Continue forth and you'll find two ladders going down. Destroy the wooden plank to find a switch behind it. Pull the switch to raise the iron grate which will allow you to access the ladder going up. You can find one of Jimbo's game targets there. (Penis Mouse)
After defeating the Penis Mouse, use the ladder to the far right this time. You'll find Cornwalis held captive by two hobos. Defeat them and free him. He'll be added to your Friends List as well. Destroy the wall to the left to find more items. Don't forget to loot the bodies of the hobos to get a Broken Glass weapon. Return to the previous area and take the other ladder to the left this time.
Head west and loot some items from the grate. Continue to the right and turn the yellow valve to lower the sewage level. Loot the chest to get a new weapon. Walk along the walkway and continue east this time.
Take out the hobos along the way then shoot the ladder beside the sewage pipe to lower it down. Climb up the ladder then go to the left. Continue past the open tunnel and shoot the red valve you'll come across.
Continue past the pipe and destroy the wooden plank. Enter the hole in the wall and continue heading west to find Simon. Kill the rats around him to make the mama rat appear. Make sure to hit it first to start the battle with first strike since she'll be accompanied by 5 other baby rats.
You can return to Mr. Hanky to complete the quest; however, since you're already deep in the sewers, I'll recommend continuing instead. Backtrack to the tunnel to the right and go north. In the next screen, pull the lever then destroy the wooden plank along the way. Continue to the right and enter the tunnel there.
In the next area, pull the lever to connect the two ledges via a walkway. Shoot the red valve to the right afterward. Get the items there then go down the ladder. Head to the left and take out the remaining hobos. This is also counted towards the seven homeless camps relocated.
Pull the lever to the left then go up. Next, turn the yellow valve and check the grate along the way for more items. Enter the tunnel then head west. Continue past the sewage pipe and enter another tunnel. The next ladder leads to the cavern.
Just go past the crab person for the meantime since you don't have any means of reaching it yet. Continue to the far right until you reach the ladder. This is an alternate exit that will take you right outside the cinema. Another one of Jimbo's game targets are located in the lower path. Place the bait there to summon the Fruit Bat. After defeating it, you can climb up the ladder to leave the area.
Return to the sewer using the original entrance and talk to Mr. Hanky to complete the quest and to add him and his missus as friends.