Given your situation, here's my advice.
- Make sure the novel you're going to pitch is as perfect as you can make it. Agents (or worse, agents' assistants) read with the idea of finding something that will let them reject the book, so they can move on to the next one on the giant pile. You can't give them anything to use. As they say, "The first sentence has to be the best you've ever written, and every one after that has to be better than the last."
- You have to jump through whatever hoops your desired agents want you to jump through. Give them exactly what they want, when they want it. Be eager, positive, gently persistent. (For example, if an agent says to expect she'll get back with you within 30 days, after forty-five shoot her an email asking about progress.)
- Query letters are the second hardest thing to write. (In my opinion, synopses win by a wide margin.) Here's what I did and recommend everyone do: lead with your greatest strength. Start with why you are querying her, and it should be a good reason, like your book is very much like Author X, who she represents, or something equally compelling. Get the genre and word count out of the way, and then wallop her with the greatest thing about your book. That might be an award it won, a blurb from a respected novelist who writes something similar, or the killer hook. The best thing I've found is starting with "Author Y recommended I query you because ..." (Even if you don't have a personal relationship, if you ask writers for agent recommendations, most would accommodate you.) Then hit that killer hook.
- Knowing writers who write what you do is always helpful. They can open doors. Even the mention of their names will open doors.
- A great hook is essential. Can you make your story compelling in just a few words? My agent is going to be pitching the book I'm working on right now as "Huck Finn meets Goodfellas." Two dissimilar works, but both interesting and successful, and it sounds like a book I'd want to read. If an agent you're querying thinks the hook is compelling, she's going to want to read the book.
- This is the most important piece of advice, so burn this one into your retinas. If you are set on being traditionally published, you can't give up. Ever. I got lucky. In 2009, when the publishing industry was completely in the toilet and virtually no new authors were getting contracts, I got a two-book deal with St. Martin's only 4 months after I finished the book and started querying. Now, I think it's a good book, but there were a lot of other good books being rejected. The reason I got the contract was that I happened to be in the right place at the right time. I queried an agent the day after she'd had lunch with an editor looking for a book like mine. Had I queried her two days earlier, she might have remembered that letter. Maybe. A week earlier, I wouldn't even have registered. I've seen a lot of agents going through queries at conferences. They give them 5-10 seconds before they move on to the next. Don't let that depress you. This - and only this - might be why you haven't gotten picked up. You have to keep querying. There are a lot of agents out there, and they all want to sell a new book. Send out 10 queries. If you don't get at least a couple of requests for material, rework your letter and send out 10 more. Keep going. Fine tune. If you've tried them all, start over with a different book. You have at least two that sound ready.
Keep track of who responds (I used a spreadsheet) and then throw away or delete the rejections. Negative thoughts are not allowed. You are an author. You just have to make the rest of the world realize it.
And nobody is going to do that but you.