The Short Version
Kaine and Sid have been hanging out for some time in Waterdeep, solving crimes and crackin' clues. Penny joined them some years back. They fought a giant stone monster outside the city, and prevented a bunch of terrorists from doing bad stuff. Later, Penny and Kaine went to hell (or so they thought) to rescue his brother Adrian. Turns out "hell" is a verdant world, free of magic and men, where an ancient elf lord was trapped 10,000 years ago. Evil elf used a fallen celestial's power to empower Kaine's bloodline. Evil elf's friends tricked Kaine's people centuries ago into thinking a magic sword was good, but it was actually the key to setting evil elf free, so when Kaine stabbed him, he did just that. But just before evil elf could return to the world, Kaine closed the portal, trapping everybody in the prison planet.
Then, it turned out the prison planet was a twin to our world, representing its natural state, uncorrupted by mortal magic, separated from its counterpart by elf magic. Gods explained to the heroes that the two worlds had to be reunited, or their homeworld would wither and die due to magic abuse. They gathered allies, and did a big magic thing, and the worlds crashed together, reuniting...and setting off a minor apocalypse: the Spellplague.
In 1385 (3 years ago), the Spellplague began. Some land features were altered, and a great many monsters were birthed. Most magic users couldn't use their magic safely anymore--a lot of them died. Witches, warlocks, druids, and clerics (in the presence of their gods) were fine. Artifice rapidly rose to replace magic in most people's lives. Within the first year, most of the chaos had died down. People still hire adventurers to hunt down monsters (well worth it, since their essences power Artifice), but big cities are pretty much safe. Magic users have found ways to use magic again, but Artifice is more convenient in most cases. Some political power changed hands, but the world avoided all-out war.
Penny has become this world's Henry Ford, rapidly industrializing Waterdeep and the surrounding area. When the city's magical lights failed, making the streets deadly monster havens every night, her streetlights brought safety to the city. The walls are defended by cannons that can take down any monstrous horde from afar. Thousands of farm folk, displaced from their lands by roving monsters, have found lucrative work in her factories. Towers have been erected to dock airships, which carry goods far inland, where the seafaring merchants can't reach, high above the danger of monsters and men.
While he enjoyed a few years of high adventure, chopping down monster after monster, Kaine has mostly returned to his day job, investigating mysterious incidents, finding lost children and wayward lovers, and generally doing the private eye gig. That is, when he isn't taking care of his own monstrous horde--Penny's children, whom she has little time to spare for.
And so Kaine, Sid, and INSERT MYSTERY MAN HERE are back in action, just in time for a mysterious femme fatale to arrive with a simple job, that's sure to spiral into all kinds of trouble.