If you've finished a manuscript and think it's ready to submit, your timing at this moment in the history of book publishing is unique. On the one hand, the "old school" brick and mortar publishing houses of New York are still buying and producing books. However, they are far more cautious about their bottom line. The days of big advances--or even modest ones--are gone unless you are Jackie Kennedy. In a nutshell, it's simply more difficult these days to attract the attention of Simon & Schuster or HarperCollins or the like for a first novel.
Working in your favor is the rise of smaller, quality presses and "imprints" of larger publisher. An "imprint" is a small publishing venture, nearly always created by a venerated professional editor, within a larger publishing house. An "imprint" is a kind of reward for a successful professional career in publishing. Often the imprints specialize in certain types of novels that are dear to the heart of the main editor--which means you need to do you research before submitting to an imprint publisher. There are also smaller, indie presses that publish a few titles a year, and will sometimes take a chance on a first novel. A small press might print only a few hundred copies, but do so with the knowledge that lightning can strike: the title wins some awards, creates some buzz, grows "legs" (as they say in publishing) and starts to sell well.
But say you get no response from the Big Six publishers in New York, and not a peep from the imprints and small presses or agents. Luckily for you, there is Amazon and Kindle and the whole new world of e-publishing. There are just enough success stories (Amanda Hocking, for example, the mom from Minnesota and her fantasy series) to make e-publishing attractive. A whole new layer of jobs in publishing has arisen: formatting and design for e-publication. You can send your manuscript via email to any of one of hundreds of little "companies" (often they are a person or persons working from home). They will prepare for your novel for Kindle or other formats and charge you anywhere from $150 to several hundred dollars depending on what you want. Then you "Kindle-ize" your novel, sit back, and wait for the royalties to roll in. As an add for Lotto goes, "It COULD happen."
But it probably won't. There is a great flood of low quality, self-published e-lit that makes it extremely hard for your novel to the attention it so richly deserves :-).
My advice at this moment? Don't be in a hurry to go the e-pub route. Try to get at least some traction in the print world. If you're getting absolutely no response from print editors, your writing is probably not competitive. Sorry, but this needs to be said. If your writing is competitive an editor, even a junior assistant to the assistant editor going through the slush pile will spot it. And it will be far easier to sell your books and make a buck in the new, e-pub world once you've proven that you can compete in the old school world of ink on paper.