I have a 99 3.0 v6 and I have 33s and like 5 inches of lift, and it's a manual but it has an extremely hard time gaining speed after 60mph and I have 3.73 gears will swapping out for a 4.10 axle help me gain speed so I can drive on the interstate?

 

Yes, it will help and 4.56 would be better

Do you have a manual or automatic?

The 3.0l Vulcan engine is a High RPM engine by Design
You need to be at 3,500RPMs to have any power/torque, most engines do this at 2,500rpm

So you NEED to keep the RPMs above 3,000 at least, so down shift to lower gears, and do not use OverDrive(OD) at all with 33" tires and a 3.0l Vulcan engine

You can go here and plug in some numbers: https://www.crawlpedia.com/rpm_gear_calculator.htm

3rd on a 4-speed or 4th gear on a 5 speed is 1.0 ratio, OD is .78 ratio

You need to be at 3,000rpm at least, closer to 3,500 is better

So 4.56 would be best for the 3.0l Vulcan and 33" tires

With the 3.73 at 60mph you would be at 2,300rpm in 3rd/4th, 1,200rpm BELOW peak power band, so no surprise you have no power

 

Well, I've got the 4.0l sohc, so I can't say for sure how helpful this will be to you. However, I've got 32" tires and a 4" suspension lift and with 4.10 gears I have to push it to 3500 rpm in 4th to get above 70 in fifth if I'm going up hill, say an 8° climb. On flat ground I'll shift at around 3000 for the 3-4 and 4-5 shifts if I plan on doing 70 or more. The 4.10 gears and 4.0l will get the truck to 65 without ever going over 2500 rpm, but I feel live I've gotta really get on it if I wanna do 70+. Just my 2 cents