Originally there were two builds of NppExec: the Unicode build and the ANSI build. The Unicode build was compatible with Unicode Notepad++ and the ANSI build was compatible with ANSI Notepad++. You could check your version of Notepad++ by pressing F1 or from its main menu (? -> About Notepad++). You would see something similar to "Notepad++ v5.1.3 (UNICODE)" or "Notepad++ v5.1.3 (ANSI)". The corresponding version of NppExec (Unicode or ANSI) was required.
The Unicode version of Notepad++ was recommended. The ANSI version of Notepad++ existed just for compatibility with old non-Unicode systems (such as Windows 98 or Millenium) and with old non-Unicode plugins.
Talking about NppExec, its Unicode build is more powerful because it has a fully Unicode interface and supports input files in ANSI, UTF-8, UCS-2 LE (Unicode wide characters in Windows) and UCS-2 BE encodings. The ANSI version of NppExec supported just ANSI input files. It was caused by the following reason: conversion from UTF-8 or UCS-2 to ANSI might lead to loss of some Unicode characters which have no ANSI analogue.
Starting from Windows 2000, the operational system (i.e. Windows) itself is Unicode, which means it internally operates with Unicode characters. The next versions of Windows, such as Windows XP, Windows Vista and Windows 7, also have a Unicode core. So now, when most of the people have at least Windows 7 (or even Windows 10), there is no much sense in having a non-Unicode text editor while Windows itself is Unicode natively. So today's Notepad++ is a Unicode program, as well as NppExec, Notepad++'s plugin, is also Unicode.
With today's 64-bit (also known as "x64") CPUs and operational systems, more and more software become 64-bit. Notepad++ is also available as a 64-bit (x64) and a 32-bit (x86) application. The 64-bit Notepad++ runs under 64-bit Windows and allows to use more RAM - in practice it means you can open larger files (with the size of 1 GB and more) with it. The 32-bit Notepad++ runs under both 64-bit and 32-bit Windows and additionally supports old 32-bit plugins that have not been ported to 64-bit yet. Luckily, NppExec is available in both 64-bit and 32-bit versions, so it's up to you which version of Notepad++ to choose :)