Booking a ticket from Geneve Airport to Zermatt

I love to see the the Centovalli. But I am concern on the transfer from Zermatt to Domodossola via the Simplon Pass and Lucarno to Sondrio as we have 2 large luggages to manage.

There shouldn't be any luggage problems. The bus over the Simplon Pass accepts even bikes. There will be enough space in the Centovalli train too. The distance between the platforms of the Simplon bus and the Zermatt resp Centovalli railway is not more than 200 metres (less if you don't sit in the last wagon of the Zermatt train).
Lugano - Bernina Express: there is a direct bus (with enough luggage space!) between Lugano railway station (dp 10.00) and Tirano Bernina Express station (ar 13.00).

You're not the only one travelling with large suitcases. Trolleys that can carry your luggage are to be found at train and coach stations, there is enough room in trains and coaches for luggage. Think it over if you want to spoil your own trip because of an issue that isn't really one. This is to be meant friendly.

Edit: Oops, neckervd beat me :-)

Thanks to a_p and neckervd for advice. I will rethink my intinerary and include Centovalli.

Would I miss anything if I skip Glacier Express according to a_p suggested itinerary?

Would I miss anything if I skip Glacier Express

Not really. The most spectacular part of the Glacier Express is part of your St. Moritz - Zurich journey - only in the opposite direction. Additionally, Bernina Express is simply the best of scenic trains , believe me. Alltogether you have decided to do the ultimate combination of train routes one can do in Switzerland (and it even includes two excursions to Italy).

I'm little confused for the Zermatt -> Simplon Pass -> Domodossola. I checked the sbb.ch and was given direct train route which I believe is not the one u r refering to.

So I embark the train at Zermatt, disembark at Brig and transfer to Domodossola via bus, then take the centovalli train to Lucarno? (ZERMATT - DOMODOSSOLA via BRIG - BUS PAG - ISELLE DI TRASQUERA from sbb.ch - is this the one?).

So I embark the train at Zermatt, disembark at Brig and transfer to Domodossola via bus, then take the centovalli train to Lucarno?

That is absolutely correct! You see, little by little, you understand the Swiss and Italian geography :-)

BTW: There is indeed a tunnel under the Simplon pass (Brig - Iselle), but I would for obvious reasons not have recommended you to use it.

Now, what's your next question?

No. There are only 3 connections via Simplon Pass: Zermatt dp 7.39, 8.39, 10.39 - Brig dp 9.18, 10.18, 12.18 - Domodossola ar 11.00, 12.00, 14.00
Dp from Domodossola to Locarno: 11.25, 14.05, 15.25 (ZERMATT - LOCARNO
via VISP - BRIG - BUS PAG - DOMODOSSOLA).
Standard fare Zermatt - Locarno 113 CHF, with Swiss Half Fare Card 56.50 CHF, with Swiss Pass free.
Bus timetable: http://www.fahrplanfelder.ch/fileadmin/fap_pdf_fields/2011/12.631.pdf

Thanks for all the help. As a first timer, it's really challenging to mind thru' all the info available in the Internet. I'm used to Europe travel by car (being to some parts of Germany, Belgium, France and Austria via car), but for commuting by public transport network is a new area for me.

You're welcome. You're going to make a very pleasant experience if you travel by train. Last remark (for the moment...?): Please report back so that the community knows how your trip turned out to be.