Handloader and its' sister mod, Vigilant Recycler, add in a plethora of new rounds that do a variety of balanced murderizing.

We'll begin with some technical information on Handloader and Vigilant Recycler; Every DLC except for the preorder packs, JIPLN, NVSE, and JohnnyGuitar are all required. Aside from that, some ammunition variants are available to be purchased from vendors, and are added via script for maximum compatibility. Another neat thing is that via scripts, you'll receive damage bonuses for having Pyromaniac or Demolitons Expert with applicable ammunition (explosive or incendiary ammo).

In terms of compatibility, Handloader and Vigilant Recycler are scripted to add mass amounts of surplus/bulk ammo to vendors who already sell that, so it's compatible with mods who use vanilla formlists for vendor NPCs.
While the mod works fine almost anywhere in your load order, nearest the bottom is best if you've got a lot of mods with tweaks
In terms of "will this ammo work with this modded gun?", most of the time - yes. So long as the mod author of the gun used a vanilla formlist for the ammo *used* in the gun

As for balance -  while Handloader was initially balanced around realism in mind, that is *very* difficult to get across into New Vegas consistently; and thus currently Handloader's balance is based around the vanilla game; just expect more effective rounds to deal more damage to your gun. Personally, I use it with BLEED, and it feels fine to me.

I recommend using JIP Improved Recipe Menu and Loot Assist - Autoloot and Shared Crafting (crouch activate a standard crafting bench to store crafting ingredients)

Ammosmith adds in nearly 150 individual ammo variants for almost every single ammunition type, excluding the camera, microfusion breeder, and Archimedes II

You can expect to see a standardization of naming conventions for ammunition, crafting recipes, ammo weights, and ammo effects compared to base-game NV, as I've done a consistency pass for all ammo, ammo recipes, ammo effects, and explosions; even including DLC-added ammo

Ammunition loading has also been streamlined to prefer more "basic" ammunition first, with wilder loads being swapped to later. It should be very intuitive.

One perk has been affected: Junk rounds; with it being changed from requiring 7 luck and 45 Repair to 45 Survival and 25 Repair.

As for ammunition added, I will categorize them as neatly as I can, because there's a lot. Some stuff may be consolidated if there's either not enough to justify one category, or if there's a lot of overlap between very similar cartridges.

Shotshell


.357, .44, and .45-70


.22


5.56mm, .308, .50BMG, 12.7mm


5mm, 9mm, 10mm, .45ACP


Rockets and Missiles, Oh my.


25mm and 40mm



BB




Vigilant Recycler does a few things, it, like Handloader, modifies the script of Bulk ammo boxes to function better when purchasing multiple of the same type and provides an amount based accordingly off of box weight/ammo weight. Basic energy cells are also revalued to 1 cap per cell. 

A few more ammo types were introduced with Vigilant Recycler.
EC, ECP, MFC

• Gamma-Emitted, which require (You guessed it,) Pyromaniac. 
• Unstable, which require Vigilant Recycler. These deal massive damage, but the discharge of energy has a chance to radiate back at you, harming you.
• Taze rounds, which add fatigue damage to non robotic enemies, instead dealing bonus damage to them.

Flamer Fuel

• High-Pressure - Essentially Max Charge
• Purified - Requires Pyromaniac  - Essentially Overcharge, but extra flamey.
• Toxic Fume - Requires Chemist
• Napalm - Requires Chemist and Pyromaniac
• White Phosphorus - Requires Chemist and Pyromaniac

Another thing Vigilant Recycler does is... provide more eccentric ammo types.

• Microfusion Cells have the extremely fun Strange Matter rounds, which have a chance to instantly gib a target.
• Electron Charge Packs have the very strong Quantum rounds, which ignore 50 DT/DR.

Lastly, these unique rounds can be purchased exclusively from The Sink.
Go thank _Voidwalker, and maybe give him a Kudos for the implementation of most of Vigilant Recycler.